Sjogren's Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

SJOGREN’S SYNDROME A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Sjogren’s Syndrome: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84629-4 1. Sjogren’s Syndrome-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on Sjogren’s syndrome. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON SJOGREN’S SYNDROME ............................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Sjogren’s Syndrome ...................................................................... 5 E-Journals: PubMed Central ....................................................................................................... 35 The National Library of Medicine: PubMed ................................................................................ 36 CHAPTER 2. NUTRITION AND SJOGREN’S SYNDROME ................................................................... 81 Overview...................................................................................................................................... 81 Finding Nutrition Studies on Sjogren’s Syndrome..................................................................... 81 Federal Resources on Nutrition ................................................................................................... 89 Additional Web Resources ........................................................................................................... 90 CHAPTER 3. CLINICAL TRIALS AND SJOGREN’S SYNDROME .......................................................... 91 Overview...................................................................................................................................... 91 Recent Trials on Sjogren’s Syndrome.......................................................................................... 91 Keeping Current on Clinical Trials ............................................................................................. 98 CHAPTER 4. BOOKS ON SJOGREN’S SYNDROME............................................................................ 101 Overview.................................................................................................................................... 101 Book Summaries: Federal Agencies............................................................................................ 101 Chapters on Sjogren’s Syndrome ............................................................................................... 102 CHAPTER 5. PERIODICALS AND NEWS ON SJOGREN’S SYNDROME .............................................. 105 Overview.................................................................................................................................... 105 News Services and Press Releases.............................................................................................. 105 Newsletter Articles .................................................................................................................... 107 Academic Periodicals covering Sjogren’s Syndrome ................................................................. 109 CHAPTER 6. RESEARCHING MEDICATIONS .................................................................................. 111 Overview.................................................................................................................................... 111 U.S. Pharmacopeia..................................................................................................................... 111 Commercial Databases ............................................................................................................... 112 Researching Orphan Drugs ....................................................................................................... 112 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 117 Overview.................................................................................................................................... 117 NIH Guidelines.......................................................................................................................... 117 NIH Databases........................................................................................................................... 119 Other Commercial Databases..................................................................................................... 121 APPENDIX B. PATIENT RESOURCES ............................................................................................... 123 Overview.................................................................................................................................... 123 Patient Guideline Sources.......................................................................................................... 123 Associations and Sjogren’s Syndrome ....................................................................................... 127 Finding Associations.................................................................................................................. 129 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 131 Overview.................................................................................................................................... 131 Preparation................................................................................................................................. 131 Finding a Local Medical Library................................................................................................ 131 Medical Libraries in the U.S. and Canada ................................................................................. 131 ONLINE GLOSSARIES................................................................................................................ 137 Online Dictionary Directories ................................................................................................... 138 SJOGREN’S SYNDROME DICTIONARY ............................................................................... 139

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INDEX .............................................................................................................................................. 199

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with Sjogren’s syndrome is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about Sjogren’s syndrome, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to Sjogren’s syndrome, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on Sjogren’s syndrome. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to Sjogren’s syndrome, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on Sjogren’s syndrome. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON SJOGREN’S SYNDROME Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Sjogren’s syndrome.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and Sjogren’s syndrome, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “Sjogren’s syndrome” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Sjogren's Syndrome Comes of Age (editorial) Source: Seminars in Arthritis and Rheumatism. 28(6): 355-359. June 1999. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. Website: www.wbsaunders.com. Summary: Primary Sjogren's syndrome (SS) is an autoimmune exocrine disease characterized by salivary and lacrimal gland destruction progressing to xerostomia (dry mouth) and xerophthalmia (dry eyes or sicca symptoms). Nevertheless, any exocrine as well as nonexocrine organ may be involved. Dryness is not solely a result of glandular destruction; cytokines, autoantibodies, and other soluble factors may be also involved. In this article, the authors propose a two stage model of SS pathogenesis in which the

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Sjogren's Syndrome

initial process seems to be increased epithelial cell apoptosis leading to autoantibody production and subsequent salivary gland lymphocytic infiltration. Treatment of SS includes patient education, prevention, tear and saliva substitution, exocrine glands stimulation, and immunointervention. Pilocarpine, a natural alkaloid and stimulator of muscarinic receptors in exocrine glands, is an effective agent for the treatment of sicca symptoms (abnormal dryness of mucous membranes). Another systemic stimulatory agent to treat sicca symptoms is cevimeline, a quinuclidine derivative of acetylcholine. The authors conclude that molecular understanding of the biological mechanisms that lead to tissue damage in SS may lead to newer biological treatment for this common and disabling illness. 2 figures. 1 tables. 29 references. •

Whole Saliva and the Diagnosis of Sjogren's Syndrome: An Evaluation of Patients Who Complain of Dry Mouth and Dry Eyes. Part 1: Screening Tests Source: Gerodontology. 13(1): 35-43. July 1996. Contact: Available from FDI World Dental Press Ltd. 7 Carlisle Street, London W1V 5RG, United Kingdom. Summary: Sjogren's syndrome (SS) is a common autoimmune disorder characterized by generalized desiccation, exocrine hypofunction, and serologic abnormalities. More than 90 percent of SS patients are women. This article reports on a study undertaken to determine if whole saliva can be used to diagnose SS. The study included 49 subjects (48 female, 1 male) with a mean age of 54 years (plus or minus 13 years). In order to be admitted into the study, the subjects had to complain of dry mouth and dry eyes. Whole saliva was collected by the spitting method. Tests were used to measure the salivary flow rate, pH, buffer capacity, lactobacillus concentrations, yeast concentrations, and protein, albumin, sodium, and amylase activity. Based on the sialometric (salivary measurements) findings, the patients were divided into 3 groups: group 1 contained those with abnormally low resting (RFR) and stimulated (SFR) flow rates; group 2 contained those with a low RFR but normal SFR; and group 3 contained those with normal salivary flow rates. The group 1 patients were unique: their saliva demonstrated a low pH and buffer capacity, high lactobacillus and yeast concentrations, decreased protein output and amylase activity, and elevated albumin and sodium. Moreover, virtually all of them had abnormally low lacrimal flow rates. The authors conclude that these findings suggest that whole saliva could be used to provisionally diagnose SS. Critical to this diagnosis was an abnormally low stimulated whole saliva flow rate. 6 tables. 26 references. (AA-M).

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Management of Sjogren's Syndrome in Dental Practice Source: JADA. Journal of the American Dental Association. 132(10): 1409-1417. October 2001. Contact: Available from American Dental Association. ADA Publishing Co, Inc., 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2867. Website: www.ada.org. Summary: Sjogren's syndrome (SS) is a multisystem inflammatory disorder of the exocrine glands (including salivary glands) with a wide range of extraglandular involvement. Symptoms of dry eyes and xerostomia (dry mouth), although not invariably present, are characteristic features of SS. An increased risk of oral and dental diseases is a prominent consequent of SS. The author of this article reviewed recent medical and dental studies that have advanced the understanding of the causes and treatment of SS. The author focused on studies addressing the diagnosis and treatment of the oral component of the disease. SS is a widely underdiagnosed disease. A delay in

Studies

5

the diagnosis of SS may have a significant physical, psychological, and economic impact on the affected person. The pathogenesis (development) of SS appears to involve a number of factors: immunological, genetic, hormonal, and possibly infectious. Impairment of salivary function in SS increases the risk of developing oral diseases. Effective management of oral health comprises enhancement of salivary output (cholinergic agonist drugs such as pilocarpine or cevimeline) and prevention and treatment of dental caries (cavities), oral candidiasis (thrush), and allergic mucositis. Periodic evaluation of various clinical and laboratory parameters is needed to monitor disease status. Successful management of SS requires a multidisciplinary approach, and the dentist plays an essential role in the diagnosis and treatment of the disease. 4 figures. 3 tables. 65 references. •

Reliability and Sensitivity of Diagnostic Tests for Primary Sjogren's Syndrome Source: Journal of Rheumatology. 26(3): 604-608. March 1999. Contact: Available from Journal of Rheumatology. Subscription Manager, 920 Yonge Street, Suite 115, Toronto, ON M4W 3C7. (416) 967-5155. Fax (416) 967-7556. Summary: This article reports on a study undertaken to investigate whether diagnostic tests for primary Sjogren's syndrome (pSS) are reproducible when repeated after one year (reliability) and to evaluate whether the sensitivity of the diagnostic tests increases with repeated testing (sensitivity). A structured interview investigating the subjective sensations of dry eyes and dry mouth, and diagnostic tests were performed twice, with a one year interval in 66 patients with pSS. Reliability was given as the percentage of positive tests remaining positive at the second examination, while sensitivity was given as the percentage of patients with positive tests. Highest reliability was obtained for the sensation of dry mouth (98.2 percent), sensation of dry eyes (96.4 percent), and anti SSA or SSB antibodies (93.3 percent). Lowest reliability was obtained for rheumatoid factor at cutoff titer 1:32 and positive Schirmer I in one eye (77.4 percent). The pooled sensitivity for all the diagnostic tests increased significantly compared to the examination, which had the lowest sensitivity. The authors conclude that the diagnostic tests for pSS are generally highly reliable when performed twice with a one year interval. The gain in sensitivity by repeating the tests is limited. 1 table. 17 references.

Federally Funded Research on Sjogren’s Syndrome The U.S. Government supports a variety of research studies relating to Sjogren’s syndrome. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to Sjogren’s syndrome.

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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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Sjogren's Syndrome

For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore Sjogren’s syndrome. The following is typical of the type of information found when searching the CRISP database for Sjogren’s syndrome: •

Project Title: AIRWAY SURFACE LIQUID COMPOSITION OF HUMANS IN VIVO Principal Investigator & Institution: Knowles, Michael R.; Professor; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2003 Summary: The long-term goal of this project is to better define the role of normal airway epithelial ion (and water) transport in lung defense, and identify the primary (and other early) pathogenic events in CF lung disease. The overall hypothesis of this proposal is that the surface epithelia in normal airways exhibit "isotonic volume absorption", and the primary pathophysiologic event in CF lung disease involves accelerated absorption of isotonic liquid, which limits the normal hydration of mucus in conduct airways. Mucus stasis ensures, with impaction in small airways and predisposition to chronic bacterial infection. We will specifically address an alternative hypothesis, which suggests that normal airways absorb ions, but not volume, and generate a hypotonic airway surface liquid (ASL). Under the "hypotonic ASL" paradigm, the pathogenesis in CF airways is similar to that of the sweat duct, i.e., an inability to absorb NaCl, which results in higher concentrations of salt relative to normal, and inhibition of salt-sensitive small-peptide anti-microbial activities. We will use specific techniques in vivo, including ion-selective electrodes, to study and lower airway epithelial function and ASL composition. We will study normal subjects, CF patients (including infants and neonates), and pertinent disease-control groups, including patients with pseudohypoaldosteronism (PHA) and Sjogren's syndrome. These studies are designed to define the relative contribution of surface epithelia and SMGs to ASL metabolism, in part to test theories related to SMG dysfunction in the pathogenesis of CF airway disease. We will measure the water content (percent solids) of airway secretions in CF and normals to test the hypothesis that accelerated isotonic volume absorption leads to reduced hydration of mucus in CF. Pertinent data will also be generated that address the role of specific inflammatory or neutrophil functions in early pathogenesis. Finally, studies of BAL in CF infants and neonates will directly test whether mucus obstruction precedes infection, or whether infection occurs first. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: APOPTOSIS IN SJOGRENS SYNDROME Principal Investigator & Institution: Rosen, Antony; Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-MAY-1998; Project End 31-JAN-2007 Summary: Sjogren's syndrome is a chronic autoimmune disease, which results in decreased secretion from salivary and lacrimal glands. The broad, long-term objectives of this proposal are to define pathogenic mechanism(s) in Sjogren's syndrome, with a view to identifying relevant pathways for therapeutic intervention in this disease. Recent studies have implicated abnormal cholinergic signaling and the cytotoxic lymphocyte granule pathway as areas of potential importance in this regard. This proposal will focus on these pathways in Sjogren's syndrome, by defining the mechanisms by which granzyme B (GrB) induces salivary gland epithelial cell damage and dysfunction and autoantibody production. The specific aims of the proposal are to

Studies

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(1) Define the mechanisms and functional effects of type 3 muscarinic acetylcholine receptor (M3R) cleavage by GrB. This will be done by elucidating GrB-induced cleavage of M3R that occurs in intact cells during granule-induced cytotoxicity, and addressing the effects of GrB cleavage on M3R ligand binding and signal transduction; (2) Identify the predominant mechanisms of salivary epithelial cell damage and dysfunction in vivo in patients with Sjogren's syndrome. Specific evidence of GrB- generated fragments of Sjogren's syndrome autoantigens in affected tissue from patients with Sjogren's syndrome will be sought, using novel antibodies that are highly specific for neoepitopes generated by GrB-mediated cleavage. The frequency of antibodies to the M3R in patients with primary or secondary Sjogren's syndrome will be quantitated; and (3) Establish the role of GrB in the development of salivary gland dysfunction and damage in animal models in vivo. This will be accomplished by studying the development of a Sjogren's syndrome-like phenotype (inflammatory infiltrates, autoantibodies and secretory dysfunction) in wild-type and GrB-deficient NOD mice, and addressing whether immunization with granule-killed primary salivary epithelium results in an autoantibody response against salivary gland epithelial cell GrB substrates, including M3R, with functional consequences. These studies will yield an enhanced understanding of the mechanisms whereby the cytotoxic lymphocyte granule pathway participates in the pathogenesis of Sjogren's syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AQUARPORIN WATER CHANNEL PROTEINS IN EYE Principal Investigator & Institution: Agre, Peter C.; Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-FEB-1996; Project End 30-JUN-2006 Summary: (provided by applicant): Numerous physiological and pathophysiological processes involve the transport of water across cell membranes. The molecular identity of water transporters became known with discovery of the aquaporin family of membrane water channels. Four of the ten known mammalian aquaporins are expressed in anterior segment of eye. This application addresses the molecular mechanisms regulating function of human AQPO, AQP1, AQP3, and AQP5 and dysfunction of these proteins in clinical disorders of eye. Aim I. Analysis of aquaporin proteins in normal human eye. New reagents will be prepared including plasmids encoding wild-type, sitedirected mutant, and epitope-tagged human AQPO, AQP1, AQP3, and AQP5. Antibodies specific for the N- and C-termini of the human proteins will be raised in rabbits and affinity-purified. The biophysical functions of human aquaporins will be expressed in Xenopus laevis oocytes and analyzed at baseline and after activation. Human aquaporins will be expressed in yeast and purified for reconstitution into proteoliposomes for permeation studies, into planar bilayers for analysis of electrophysiological properties, and into membrane crystals for structural studies. The distribution of these aquaporins will be defined in normal human eye. Aim II. Analysis of aquaporin proteins in clinical disorders of eye. The distribution of human aquaporins will be defined in tissues from patients with cataract or Sjogren's syndrome. Basic mechanisms by which AQPO and AQP5 may contribute to these disorders will be sought including defects in water and solute permeation, membrane trafficking, subunit oligomerization, and internalization, Physiological deficits will also be evaluated in rodent models of AQPO degradation and AQP5 deficiency. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Sjogren's Syndrome

Project Title: BASAL-LATERAL/ENDOMEMBRANE TRAFFIC IN LACRIMAL ACINI Principal Investigator & Institution: Mircheff, Austin K.; Professor; Physiology and Biophysics; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-APR-1985; Project End 31-MAR-2004 Summary: (provided by applicant): Primary Lacrimal Deficiency and Sjogren's autoimmune dacryoadenitis are more common in women than men, and the same constellation of hormonal factors, i.e., insufficient bioavailable testosterone and excessive prolactin, may contribute to both pathologies. Lacrimal insufficiency also may occur after refractive surgery. Sjogren's autoimmunity targets the M3 muscarinic receptor, a cell surface protein, and various intracellular proteins. An emerging understanding of traffic between the basal-lateral plasma membranes and endomembrane compartments suggests the immune system may lose its tolerance for familiar proteins, or become activated against cryptic proteins, when: (a) changes in traffic increase the rates at which acinar cells express intracellular autoantigens at their blm or secrete them to the interstitium; (b) acinar cells begin to express MHC Class II molecules and present autoantigen peptides directly to CD4 T cells; or (c) the spectrum of immunomodulatory factors acinar cells secrete to the interstitium becomes immunostimulatory instead of immunosuppressive. In vivo experimental perturbations that alter blm / endomembrane traffic include: chronic and supramaximal secretory stimulation, which might arise in vivo as the lacrimal gland - ocular surface servomechanism compensates for lacrimal dysfunction due to androgen insufficiency or prolactin excess; stimulation with epidermal growth factor (EGF), which may be elicited in vivo in response to corneal trauma; and culture in the presence of prolactin, which may mimic high prolactin states. The specific aims of the proposed work are to: 1. Identify membrane protein sorting mechanisms that are altered when lacrimal acinar cells are stimulated with (EGF). 2. Map the traffic of M3 cholinergic receptors; test the hypotheses that acinar cells secrete M3 proteolytic fragments to the interstitium; that acinar cells present M3 peptides to CD4 T cells via MHC Class II molecules; and that chronic stimulation with carbachol decreases M3 receptor turnover, potentially decreasing M3-related antigenic stimulation. 3. Test the hypotheses that a milieu containing excessive prolactin alters protein sorting in the absence and presence of cholinergic stimulation and that excessive prolactin increases turnover of M3 receptors, potentially increasing M3-related antigenic stimulation. 4. Map the traffic of endogenously expressed IL-2 and transduced anti-inflammatory cytokines, such as IL10. Test the hypotheses that IL-10 alters traffic of endogenous proteins; that chronic stimulation with carbachol in the absence of androgens increases traffic of IL-2 and IL-10 via the apical secretory pathway; and that chronic carbachol stimulation in the presence of androgen increases secretion via the blm. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CAN AUTOIMMUNITY

SOMATIC

MUTATIONS

MEDIATE

ANTI-LA

Principal Investigator & Institution: Farris, a Darise.; Assistant Member; Oklahoma Medical Research Foundation Oklahoma City, Ok 731045005 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): The mechanisms of clinical autoimmune disease have proven to be difficult to elucidate. Evidence implicating molecular mimicry, sub-

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dominant epitopes, immune ignorance, and failure of the apoptotic cellular apparatus as contributing to the mechanisms of autoimmunity have been convincingly demonstrated in various experimental systems. Perhaps, other mechanisms exist. We propose that somatic mutation is a possible mechanism to initiate autoimmunity and further propose to experimentally evaluate an example of autoimmunity to the nuclear antigen La, which is targeted in Sjogren's syndrome and systemic lupus erythematosus. Presumably, the new protein structures created by somatic mutation would have been previously unknown to the immune system. Once the efferent immune response against the new structure(s) extends to non-mutated structures of the antigen, then an autoimmune response would be established. Serendipitously, we detected examples of somatic frame shift mutations in a mutational hot spot of human La in anti-La precipitin-positive patients at both the DNA, RNA and protein level. Recent preliminary data indicate that such mutations may occur in up to 50% of La positive patients, while no mutations were detectable in healthy donors and age-, sex-, and race-matched controls. Insert or deletion in the hot spot leads to a subsequently altered amino acid sequence with truncation of the La antigen. Such mutations could result in novel B- and T-cell epitopes. Indeed, we found antibodies to the hot spot region in autoimmune patients. Furthermore, we created genomic mutant and native La gene constructs and established transgenic animals in which these constructs were permanently expressed. These genomic constructs will be used to create a genomic clone allowing us to develop an animal tolerant to native human La in which we can switch on the expression of the human mutant La form. We herein present an experimental plan to further explore somatic mutation of La and its potential for generating autoimmunity. We have developed highly sensitive and specific assays to detect the somatic mutation at the DNA, RNA and protein level. According to power calculations we will extend our preliminary studies by applying these techniques to anti-La positive and anti-La negative age-, sex- and race-matched patients as well as healthy controls. Furthermore, we will determine whether or not somatic mutation in La can create novel B- and T-cell epitopes in experimental animals and autoimmune patients. Finally, using the Cre loxP system we will generate an animal model imitating the particular somatic mutations observed in man. These experiments should help establish whether somatic mutation is a plausible mechanism for autoimmunity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENT AUTOIMMUNE DISEA

OF

SCREENING

FOR

POSTPARTUM

Principal Investigator & Institution: Smallridge, Robert; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002 Summary: Considerable evidence suggests postpartum thyroid disease (PPTD) is autoimmune in origin. Thyroid antibodies are positive in 2.8 to 18.7% of all postpartum women. The antibody titer predicts the likelihood of a woman developing clinical disease. Future studies should determine how to improve the utility of antibody testing. Postpartum enhancement of autoimmunity is not limited to thyroid diseases; flare-ups of systemic lupus erythematosus and an increase in DNA antibodies can occur. One woman with PPTD also developed a transient sicca syndrome, suggesting immunologic changes postpartum may induce an autoimmune exocrinopathy. Racial differences exist for some autoimmune diseases. One study reported 8.8% of Caucasians, but only 2.5% of African-American women were antibody positive two days postpartum. This protocol will follow 1,280 women (640 Caucasians, 640 African-American) from first

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Sjogren's Syndrome

pergnancy visit until six months postpartum. Main end-points are serum TSH, thyroid peroxidase, thyroglobulin, and Ro and La antibodies. It is expected that 64-102 women (5-8%) with thyroid autoimmunity be identified. Approximately half (32-51) women will develop clinical disease and benefit from diagnosis and treatment. The primary endpoint is to see whether there is a significant difference in the frequency of postpartum thyroid diseases between Caucasian and African-American women. A second end-point will be to assess whether postpartum women develop immunologic evidence of Sjogren's disease. The results will help to define better risk guidelines and provide improved counseling to women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENDER, SEX STEROIDS AND DRY EYE SYNDROMES Principal Investigator & Institution: Sullivan, David A.; Schepens Eye Research Institute Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 30-SEP-1985; Project End 30-NOV-2006 Summary: (provided by applicant): The preocular tear film plays a critical role in maintaining ocular surface integrity, protecting against microbial challenge and preserving visual acuity. Tear film dysfunction, in turn, may severely impact the eye and lead to desiccation of the corneal epithelium, ulceration and perforation of the cornea, an increased incidence of infectious disease, and pronounced visual impairment and blindness. Countless people suffer from tear film disorders, which are termed dry eye syndromes and are classified into 2 major types: aqueous-deficient and evaporative. Aqueous-deficient dry eye is due to decreased tear secretion from the lacrimal gland. An example is Sjogren's syndrome, a common autoimmune disease that afflicts primarily women and destroys the lacrimal gland. Evaporative dry eye is typically caused by meibomian gland dysfunction and may be a major cause of dry eye during menopause, use of estrogen hormone replacement therapy (HRT) and aging. The long range objectives of this grant application are to test our hypotheses that: (1) sex steroids are extremely important in the physiological regulation of the lacrimal and meibomian glands, as well as the production of the tear film; and (2) gender, sex steroid hormones, and in particular androgen deficiency, are critical etiologic factors in the pathogenesis of both aqueous-deficient and evaporative dry eye syndromes. Experimental procedures include mouse models, DNA hybridization arrays (i.e. gene chips), RT-PCR, ribonuclease protection assays, Northern, slot and Southern blots, in situ hybridization, cell cultures, immunoassays, HPLC/mass spectrometry, enzyme assays, histology, image analysis, hormone reconstitution experiments, as well as clinical studies with humans. Our specific aims are to: (1) identify the genes and proteins that mediate the gender-related differences in, and the sex steroid control of, lacrimal glands in normal and autoimmune (i.e. Sjogren's syndrome) mice; (2) identify the genes and proteins involved in the gender-associated variations in, and the sex steroid regulation of, the mouse meibomian gland; and (3) determine the specific effects of HRT use (estrogen, or estrogen plus progesterone), with or without androgen supplementation, on the ocular surface of postmenopausal women. Results from the studies should significantly advance our understanding of the processes by which gender and sex steroids influence the anterior segment of the eye. In addition, findings may have health relatedness for the eye, because they: (1) explore the regulation of the tear film; and (2) may lead to the development of specific therapies for the clinical treatment of dry eye syndromes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENE EXPRESSION PROFILING IN SJOGREN'S SYNDROME Principal Investigator & Institution: Moser, Kathy L.; Assistant Professor; Medicine; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 26-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Sjogren's syndrome (SS) is a chronic, progressive autoimmune disorder characterized by lymphocytic infiltration of the salivary and lacrimal glands with a heterogeneous constellation of extra glandular manifestations. SS may occur as the primary disease, or secondary to another connective tissue disease such as rheumatoid arthritis or systemic lupus erythematosus. The molecular events that lead to SS are poorly understood but thought to involve multiple components of immune dysregulation. Our overall goal is to define important biological pathways that are dysregulated in SS patients using microarray technologies to examine genomic-scale gene expression profiles. We have recently established that differential gene expression patterns can be identified using peripheral blood mononuclear cells and initial analyses to date suggest that dysregulation of interferon-inducible genes may be important in SS. Here, we propose to define gene expression signatures in a large cohort of weft characterized SS patients, evaluate potential correlations between gene expression signatures and various phenotypic components of disease, and examine the durability and relationship with disease manifestations of the gene expression signatures over time. We will also collect essential biological samples that will allow a variety of confirmatory studies to be conducted using complementary methods. Characterization of gene expression profiles in SS has a high likelihood of conferring novel and important insights in the pathophysiologic mechanisms of this disease, and providing an important source of potential targets for development of novel diagnostic and therapeutic approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC ASSOCIATION IN SJOGREN'S SYNDROME Principal Investigator & Institution: Harley, John B.; Professor; Oklahoma Medical Research Foundation Oklahoma City, Ok 731045005 Timing: Fiscal Year 2004; Project Start 01-DEC-2003; Project End 30-NOV-2008 Summary: (provided by applicant): We propose to identify genes that confer risk for Sjogren's syndrome. For the past ten years, we have been using the advances of the genomic revolution to pursue the genes that predispose to systemic lupus erythematosus. At this juncture, we have established more than 20 genetic effects for lupus and have independently confirmed six of these (see Preliminary Data). Now, a decade after starting the lupus genetics studies, we are ready to begin work with Sj gren's syndrome, a closely-related disorder. Our progress with Sjogren's syndrome will be accelerated because of the infrastructure available and our experience with lupus. We plan to build the scientific organization that will allow us to evaluate 100 candidate genes for genetic association in 300 Sjogren's syndrome patients, their families, and matched controls. In hopes of concentrating our effort on a more genetically homogeneous phenotype, we will use the new European-American consensus criteria for primary Sjogren's syndrome, with the added requirement that all affecteds evaluated have anti-Ro autoantibody precipitins. We propose to use a genetic association approach in an experimental design that will lead to gene identification by the following experimental steps: assembling the materials from probands, family members and controls; constructing the clinical and demographic database; and genotyping polymorphisms in and nearby candidate genes. Our longer term goal is to

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Sjogren's Syndrome

perform a reasonably powered genome scan for genetic association, but the technologies and methodologies are not yet proven practical. Consequently, we envision a commitment to this scientific problem over the next decade to accomplish this goal, as may be required. On the other hand, by assembling the needed materials and pursuing candidate genes, we will be specifically poised to exploit a genome scan for genetic association in Sj gren's syndrome as soon as it is practical to perform. Meanwhile, we will evaluate as many candidate genes as is practically possible with the resources made available to us and with the technologies and methods in hand to elucidate the genetic component of the etiology of Sj gren's syndrome would provide important new insights into pathogenesis, thereby providing new diagnostic capabilities and previously unexplored therapeutic targets. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GORDON CONFERENCE, SALIVARY GLANDS & EXOCRINE SECRETION Principal Investigator & Institution: Castle, J. David.; Professor; Gordon Research Conferences Box 984, 512 Liberty Ln West Kingston, Ri 02892 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2003 Summary: (provided by applicant): This application seeks support for the fourth Gordon Research Conference on Salivary Glands and Exocrine Secretion to be held February 2-7, 2003 at the Holiday Inn in Ventura, California. The conference will provide a forum for presentation and extensive discussion of the most recent progress in understanding the molecular basis of development, function and dysfunction of salivary and related exocrine glands. The general theme of this conference is on the development and polarized function of epithelial cells and glandular tissues. Individual sessions will highlight new insights concerning molecular and cellular interactions underlying the origin of epithelial polarity; glandular morphogenesis and maintenance; protein, fluid and electrolyte secretion; transport dysfunction in diseases involving epithelia; spatial organization of intracellular signaling and polarized membrane trafficking; and clinically observed glandular dysfunction. To the extent possible, sessions will integrate mammalian and invertebrate experimental systems to capitalize on the respective facile genetic and biochemical/physiological approaches toward the common understanding of evolutionarily conserved events and functions. Keynote addresses will feature established investigators of international stature who encompass the general theme in the areas of development of epithelial polarity, the fundamental basis of Sjogren's Syndrome (a Michael Humphreys-Beher memorial), and the application of functional genomics, proteomics and signaling networks in exploring glandular development and cellular function. In organizing this conference, a broad range of national and international speakers has been identified with special emphasis on promising young and newly established investigators whose research either addresses or clearly impacts on the understanding of the development and function of salivary and other exocrine glands. It is the goal of the organizing team to encourage both growth and enrichment of this important field and to stimulate new strategies for studying salivary glands. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HUMAN INTERFERON ALPHA IN TREATMENT OF PRIMARY SJOGREN'S SYNDROME Principal Investigator & Institution: Rhodus, Nelson L.; Professor and Director; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070

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Timing: Fiscal Year 2002 Summary: The hypothesis of this Phase III clinical trial is that treatment for 24 weeks with a daily dosage of 450 IU of human interferon alpha is safe and will significantly increase stimulated saliva production compared to placebo in subjects with primary Sjogren's syndrome. The primary objective will be measured by changes in stimulated whole saliva production. Secondary objectives will be measured by 100mm visual analog scales and other patient questionnaires. Change from baseline will be calculated for all secondary objective variable. The other objective is safety. This will be met by comparing adverse event reports and changes in laboratory variables. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNOREGULATORY CIRCUITS IN MAN Principal Investigator & Institution: Morimoto, Chikao; Associate Professor of Medicine; Lymphoma; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-JUL-1985; Project End 30-JUN-2004 Summary: (Adapted from Investigator's abstract): Memory CD4 T-cells play a key role in host defense as well as the triggering and maintaining of inflammation. The triggering of the costimulatory signals plays a central role in the generation of effective immune responses. The costimulatory signals can be provided by a number of accessory molecules. Of the costimulatory molecules, CD29/VLA, CD26, and CD27 have been established by this group. CD29/VLA and CD26 are preferentially expressed on CD4 memory T-cells and play an important role in the costimulation, function, and migration of memory T-cells. Much remains to be clarified regarding the complex functions of CD29/VLA and CD26 in signal transduction and the subsequent effects upon T-cell function and cell migration. The major goal of this application is to determine the immunoregulatory circuits in man. The specific aims of this application are: 1) The molecular basis of CD29/VLA in T-cell costimulation, signaling and T-cell function. They will define the structural basis of Cas-L tyrosine phosphorylation and FAK activation and define the role of Cas-L in CD29/VLA-mediated cytokine production and gene expression. Moreover, the role of Cas-L in T-cell migration will be defined. 2) The molecular basis of CD26/DPPIV in T-cell function and costimulation. The role of CD26/DPPIV in T-cell migration, the precise characteristics of the binding of ADA to CD26, and the functional significance of ADA in T-cell activation will be defined. In addition, the structure and function of the ligand of CD26 other than ADA will be defined. 3), The molecular and cellular defects in patients with autoimmune diseases. Analysis of VLA-mediated costimulation in patients with autoimmune diseases will be performed. Moreover, the expression and function, of Cas-L, and FAK as well as the migratory activity of T-cells in autoimmune diseases will be determined. In addition, the level of CD26/DPPIV in serum/plasma and its correlation with clinical complications in autoimmune diseases will be defined. The study will not only provide new insights into understanding of the mechanisms of T-cell activation and migration, but will also provide new insights into understanding the precise molecular mechanisms of immune abnormalities found in various autoimmune diseases and will lead to the development of rational therapy for the manipulation of the abnormalities found in such diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IN VIVO IMAGING OF LEUKOCYTE-ENDOTHELIAL DYNAMICS Principal Investigator & Institution: Mathers, William D.; Professor; Medicine; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): The process of leukocyte migration across the vascular endothelial barrier is fundamental to the process of inflammation and the response to infection. We will quantitate the effect of various medications such as topical corticosteroids, oral nonsteroidal anti-inflammatory drugs, and mast cell stabilizers in several of these processes. We have applied intravital microscopy in animal systems to visualize, quantitate and analyze this process. Recent advances in confocal microscopy have allowed a European group to quantitate leukocyte endothelial rolling and sticking in the microvasculature of the human eye. Combining our clinical expertise in confocal microscopy and our experience analyzing leukocyte vascular interactions, we propose to utilize in vivo confocal technology to quantitate leukocyte rolling and arrest in 4 different human vascular beds: the limbus, conjuctiva, episclera, and sclera. With these three specific aims: Aim one, we propose to image rolling and sticking of leukocytes in four different normal ocular vascular beds: the conjunctiva, limbus, episclera, and sclera. Aim two, we will compare leukocyte-endothelial dynamics in specific vascular beds in seven disease states: a) allergic seasonal conjunctivitis, b) Sjogren's syndrome and dry eye, c) blepharitis, d) graft versus host disease (GVHD), e) episcleritis, f) scleritis, and g) anterior uveitis. Aim three, we will determine the effect of medications including topical prednisolone acetate, a mast cell stabilizer (optipranolol), or an oral nonsteroidal antiinflammatory drug (indomethacin) on endothelial-leukocyte dynamics in diseases for which each is frequently prescribed. Our studies will directly clarify the pathogenesis of several troublesome and rarely studied ocular disease processes. These studies will elucidate the mechanism by which medications alter these processes. Most importantly these studies will quantitate a fundamental human biological process in microvascular beds that have not previously been imaged. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INTERACTIVE CELLULAR CONTROLS LACRIMAL GLAND FUNCTIONAL Principal Investigator & Institution: Meneray, Michele A.; Physiology; Louisiana State Univ Hsc New Orleans New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 01-APR-1987; Project End 31-JUL-2004 Summary: The long term objective of this application is to gain insight into the cellular and molecular controls of lacrimal secretion. The intent of the work is to provide a framework for understanding the pathogenesis of Sjogren's syndrome (SS) and for the development of therapies for dry-eye associated with the disease. The specific aims of this application are designed to test three hypotheses that address 1) the relationship between early changes in the lacrimal gland and the later onset of autoimmune disease and 2) the identification of the cellular and molecular mechanisms that underlie the influence of the hormonal environment on the development and treatment of SS. The first specific aim will test the hypothesis that alterations in the expression or activity of G-protein coupled receptor (GPCR) signaling molecules occur prior to lymphocytic infiltration and result in disruptions in secretion that contribute to the lacrimal insufficiency of SS. Physiologic secretory function, cell-surface receptor-G protein coupling and mRNA and protein expression of G protein subunits, and relevant isoforms of adenylyl cyclase, phospholipase C and protein kinases will be evaluated in

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pre-autoimmune genetic models of SS and in control animals. The second specific aim will test the hypothesis that the autoimmune response in SS is, in part, precipitated by inappropriate Fas/Fas L mediated apoptosis of epithelial cells of the lacrimal gland. The second aim will also test the hypothesis that the occurrence of apoptosis is influenced by the altered expression or activity of key GPCR signaling molecules. The second aim will be accomplished by the evaluation of apoptosis in lacrimal epithelial cells of genetic models of SS prior to lymphocytic infiltration. The effect of activation or inhibition of GPCR signaling molecules on the occurrence of apoptotic figures and on the mRNA and protein expression of Fas, Fas L and bcl-2 family members will be measured. Alteration of the phosphorylation state of bcl-2 family members by these treatments will also be assessed. The final specific aim will test the hypothesis that the mechanism by which androgens maintain or restore lacrimal function is by influencing the expression or function of GPCR and/or programmed cell death signaling molecules. This will be tested by acute and chronic exposure of lacrimal acinar cells to androgen. Genomic and non-genomic effects of androgen on secretory function and on the expression and activity of signaling molecules will be assessed by similar methods used to accomplish the first and second specific aims. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTRA-ORAL BIOFILM FORMATION Principal Investigator & Institution: Socransky, Sigmund S.; Professor & Head; Forsyth Institute Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): The major problems that affect the oral cavity are caused by organisms that live in biofilms colonizing the hard and soft tissues. While much has been learned about mature Dental plaque, little is known about the sequence of changes in microbial species that occurs during supra or subgingival plaque development. Even less is know about the soft tissue microbiota and the interplay between soft tissue microbiota and hard tissue microbiota during biofilm development. Two important bulk fluids, saliva and GCF, bathe the biofilm surfaces and play and undetermined role in biofilm development. Thus, the objectives of this application are to define the changes in microbial species that occur during early biofilm re-development and to evaluate factors that might influence this development including diminished salivary flow, lack of natural dentition and changes in gingival inflammatory status. SAl will compare the changes in microbial composition of developing biofilms on hard and soft tissues in 60 periodontally healthy, 60 periodontitis, and 60 denture-wearing, edentulous subjects from initial Dental cleaning to 7 days. Supra and subgingival plaque samples will be taken separately from the mesial aspect of each tooth at baseline and supragingival samples from dentures. Saliva and samples from eight oral soft tissue surfaces will also be collected. Samples will be evaluated individually for their content of 40 bacterial species using checkerboard DNA-DNA hybridization. After initial monitoring, all dentate subjects in each group will receive a Dental cleaning while dentures will be cleaned and disinfected. Thirty randomly selected subjects in each group will receive full mouth "soft tissue cleaning and disinfection. Subjects will refrain from oral hygiene for 7 days during which time Supra and subgingival plaque samples will be taken from randomly selected quadrants at 1, 2, 4, and 7 days. Denture plaque samples will be taken at the same points as saliva and soft tissue samples.SA2 will compare the microbial composition of supra and subgingival plaque, oral soft tissues, and saliva in 60 Sj gren's subjects and 60 matched controls. Full-mouth caries and periodontal status will be assessed and samples of supra and subgingival plaque will be

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Sjogren's Syndrome

taken from the mesial aspect of each tooth at baseline. In addition, eight soft tissue samples and a saliva sample will be taken. All samples will be evaluated microbiologically as described above. All subjects will receive full mouth SAP and will be re-assessed microbiologically at 28 days. The proposed study should indicate the nature of the microbial changes that occur during biofilm development on hard and soft tissues and the influence that saliva, GCF and the natural dentition have on the developing biofilms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SYNDROME

M3

RECEPTOR--DIAGNOSTIC

MARKER

FOR

SJOGREN'S

Principal Investigator & Institution: Peck, Ammon B.; Professor; Ixion Biotechnology, Inc. Box 13, 13709 Progress Blvd Alachua, Fl 32615 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2004 Summary: (provided by applicant): Sjogren's syndrome is a human autoimmune disease of the salivary and lacrimal glands that results in a debilitating xerostomia (dry mouth) and xerophthalmia (dry eyes). This syndrome may present as either a primary autoimmune disease or as a secondary autoimmune disease most often concomitant with other connective tissue diseases or diabetes. Although classified as an orphan disease, Sjogren's syndrome is grossly under-diagnosed; thus, it is estimated as many as 2-4 million individuals (90 percent of whom are women) actually have a form of this disease. At present, diagnosis of Sjogren's syndrome involves detection of lymphocytic infiltrates in biopsies of the labial glands; the presence of rheumatoid factor, serum antibodies reactive with cellular components (e.g., SS-A/Ro, SS-B/La, alpha-fodrin and/or nuclear factors), hypergamma-globulinemia, and loss of exocrine gland flow rates. None of these markers, by itself, is disease specific. Recently, we and others have shown that all sera from patients with confirmed Sjogren's syndrome contain antibody to the type-3 muscarinic acetylcholine receptor (M3R) expressed on exocrine tissues. This autoantigen, therefore, appears to be the single marker able to define autoimmune exocrinopathy. Work carried out under our Phase I grant has shown the feasibility of establishing an ELISA-based assay that utilizes a full-length recombinant form of human M3R to detect anti-M3R autoantibody in Sjogren's syndrome patients. Thus, the specific aims of this Phase II grant are to 1) complete the development of the ELISA-based assay, 2) obtain both analytical and clinical performance data for the ELISA-based assay, and 3) determine the precise association between the detection of anti-M3R autoantibody and prediction of disease in Sjogren's syndrome patients. Final development of a simple, non-surgical, Sjogren's syndrome-specific diagnostic test would be a welcome addition to the patient, the treating physician, and the clinical laboratory. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MATERNAL AUTOANTIBODIES--PATHOGENESIS OF NEONATAL LUPUS Principal Investigator & Institution: Buyon, Jill P.; Professor; Hospital for Joint Diseases Ortho Inst Orthopaedic Institute New York, Ny 10003 Timing: Fiscal Year 2002; Project Start 01-FEB-1994; Project End 15-JUN-2003 Summary: (Adapted from the Applicant's Abstract): Congenital heart block (CHB) is associated with transplacental passage of maternal autoantibodies to the ribonucleoproteins (RNP), 48kD SSB/La, and 52kD and 60kD SSA/Ro. The affected mothers might have SLE, or Sjogren's syndrome or might be asymptomatic. Why the

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developing fetal heart is specially vulnerable to such autoantibodies and why CHB occurs in the children of only a fraction of mothers with the autoantibodies, are not known. Moreover, the putative autoantigens are intracellular RNP particles, therefore it is not clear how they cause damage to the fetal cardiocytes. In Aim 1, the applicants propose to identify proteins that interact with the Ro and La RNP complexes and are selectively expressed in the human fetal heart. Novel autoantigens unique to fetal heart that are recognized by antisera from mothers of children with CHB might be discovered and a better understanding of the biological function of the Ro and La autoantigens may result from these studies. In Aim 2, the applicants will determine if the candidate autoantigens associated with autoimmune-CHB come to the surface membrane of cardiocytes during apoptosis thus being accessible to the maternally transmitted autoantibodies. In Aim 3, the applicants will develop a mouse model of CHB to understand the pathogenesis of the human disease in depth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM OF LACRIMAL GLAND SECRETION Principal Investigator & Institution: Dartt, Darlene A.; Senior Scientiist, Acting Director of Re; Schepens Eye Research Institute Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-JUN-1985; Project End 31-MAY-2006 Summary: (provided by applicant): A decrease in secretion or an alteration in the composition of lacrimal gland fluid is a primary cause of the ocular surface problems that occur in aqueous tear-deficient dry eye resulting from lacrimal gland disease, contact lens wear, LASIK surgery, and aging. Parasympathetic and sympathetic nerves are well-known stimuli of lacrimal gland secretion and the signaling pathways activated by these stimuli have been characterized. A new type of stimulus of lacrimal gland secretion, epidermal growth factor (EGF), has been identified. Based on this finding, the following working model has been proposed for the present grant: Activation of sensory nerves from the ocular surface stimulates parasymapthetic and sympathetic nerves that innervate the lacrimal gland to release their neurotransmitters. These neurotransmitters activate specific signaling pathways to stimulate the synthesis of EGF and cause its release by ectodomain shedding from the basolateral membranes. The released EGF interacts with EGF (erbB) receptors on the lacrimal gland acinar cells activating a signaling pathway that causes secretion of proteins including the shedding of EGF family members from the apical membranes. These growth factors are released into lacrimal gland fluid to protect the ocular surface. The long term goal of the experiments described in this proposal is to test this model. From the results of the proposed study, new treatments for dry eye, based on stimulating EGF-, cholinergic, and alpha1adrenergic-dependent signaling pathways to induce secretion, could be developed. To reach this goal the following specific aims have been proposed: 1) Which EGF receptor subtypes participate in stimulation of lacrimal gland secretion?; 2) Which cellular signaling pathways does EGF activate to stimulate lacrimal gland protein secretion?; and 3) How are the expression and release of EGF, transforming growth factor (TGF) alpha, and other EGF family members regulated? Acini will be prepared from rat lacrimal glands. Immunoprecipitation, Western blot analysis, immunofluorescence microscopy, and EGF receptor deficient mice will be used to determine if EGF activates and alpha1-adrenergic agonists transactivate EGF receptors to stimulate secretion. Biochemical assays, inhibitors, and adenovirus transduction will be used to determine the cellular signaling pathways activated by EGF compared to cholinergic and alpha1adrenergic agonists. lmmunofluorescence microscopy, Western and Northern blot

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Sjogren's Syndrome

analysis, and RT-PCR will be used to determine how the expression and release of EGF and its family members is regulated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF SALIVARY AND LACRIMAL INFLAMMATION Principal Investigator & Institution: Michie, Sara A.; Associate Professor; Pathology; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2005 Summary: The migration of autoreactive and effector lymphocytes from blood into salivary and lacrimal glands is a key event in the initiation and maintenance of glandular inflammation and damage in Sjogren?s syndrome. This migration involves a multi-step cascade with sequential lymphocyte/endothelial adhesion and activation events. The goals are to identify lymphocyte and endothelial adhesion molecules, chemokines, and chemokine receptors that are expressed in inflamed salivary and lacrimal glands, and to define the roles of these molecules in lymphocyte migration to these tissues. Non-obese diabetic (NOD) mice, a well-characterized model for human Sjogren?s syndrome, will be used for these studies. Specific Aim 1 will define the expression of adhesion molecules, chemokines, and chemokine receptors in inflamed salivary and lacrimal glands from NOD mice. The roles of these adhesion molecules and chemokines (and their receptors) in lymphocyte migration to inflamed glands will be assessed in functional studies in Specific Aim 2. Specific Aim 3 will determine if treatment of NOD mice with antibodies directed against adhesion molecules or chemokines defined in Aims 1 and 2 will prevent the development of salivary and lacrimal gland inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MICROTUBULE-BASED TRANSPORT IN LACRIMAL GLAND FUNCTION Principal Investigator & Institution: Hamm-Alvarez, Sarah F.; Associate Professor; Pharmaceutical Sciences; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-JUL-1996; Project End 31-MAR-2004 Summary: A major cause of ocular morbidity in the United States is lacrimal insufficiency, which affects 10 million Americans, primarily women. Approximately one fifth of these cases are clearly autoimmune- mediated and accompanied by additional symptoms which lead to the diagnosis of Sjogren's syndrome. The remainder of cases, designated as Non-Sjogren's lacrimal insufficiency, may also be mediated by the immune system. In the lacrimal gland, defects in membrane trafficking including altered processing of internalized and newly synthesized constituents through the endocytic and secretory pathways have been proposed to contribute to the development of dry eye and the autoimmune disease Sjogren's syndrome. Despite the hypothesis that defective trafficking plays a role in production of autoantigens in the lacrimal gland, little is known about the precise mechanisms by which altered trafficking patterns might occur. In interphase cells, microtubules provide a network which supports the movement of membranes driven by two different cytoplasmic motor proteins, kinesin and cytoplasmic dynein. Despite their importance in membrane trafficking, little is known about the involvement of these motors in normal and defective trafficking in the lacrimal gland. The PI has explored the membrane association and in vitro properties of kinesin from lacrimal acinar cells. Preliminary data suggest that kinesin plays a role in

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secretion under conditions that represent normal function and also under conditions in which traffic has been altered by sustained stimulation. Since such conditions may underlie the initiation of local autoimmune responses that may progress to Sjogren's syndrome or non- Sjogren's lacrimal insufficiency, these findings necessitate a more comprehensive investigation of the role of microtubule-based transport and specifically, kinesin, in lacrimal acinar membrane trafficking. The focus of this proposal is therefore: a. To identify the changes in lacrimal acinar membrane trafficking caused by disruption of microtuble-based motility. b. To define the biochemical properties and membrane interactions of kinesin isolated from lacrimal acinar cells. c. To determine whether stimulation of lacrimal secretion by carbachol, a secretagogue acting through diacylglycerol and Ca2+ -dependent pathways, alters kinesin activity. Once the function of kinesin is defined in resting and stimulated cells from normal rabbits, the PI may begin to question whether kinesin activity is altered in isolated acini from a recently described rabbit model of autoimmune dacryadenitis which exhibits features of Sjogren's syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR BASIS OF IDIOPATHIC DRY MOUTH Principal Investigator & Institution: Melvin, James E.; Interim Director; Eastman Dentistry; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: This application is for a Program Project focusing on the molecular basis for idiopathic dry mouth. The clinical entity of xerostomia or dry mouth afflicts about 3 million Americans leading to a variety of symptoms and consequences of potentially high morbidity. The impairment of salivary function comprises the sensation of oral dryness, difficulties in speech, mastication and deglutition, increased susceptibilities to oral microbial diseases such as caries and fungal infections, and reduced protection of tooth mineral. Well established causes for salivary hypofunction are side effects of medications, damage to salivary gland tissue by radiation therapy or autoimmune diseases such as Sjogren's syndrome. There is, however, a subset of xerostomic patients comprising about 20% of all dry mouth patients for whom no obvious etiology can be ascertained and these patients are therefore diagnosed with "idiopathic dry mouth". The presence or absence of objective parameters for salivary flow allows a further subdivision of idiopathic dry mouth patients. Since the underlying mechanisms for idiopathic dry mouth have not been established the therapeutic approaches available so far are only palliative at best. The studies outlined in this proposal are designed to gain fundamental knowledge at the molecular level in this area of exocrine biology. The data to be generated by the proposed studies have the ultimate goal to open new avenues for therapeutic applications. The overall aims of this Program Project is to determine the mechanisms responsible for idiopathic forms of dry mouth. There are 3 subprojects aimed at testing separate but interrelated hypotheses of salivary dysfunction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR MECHANISMS OF ION TRANSPORT BY THE SMG Principal Investigator & Institution: Muallem, Shmuel; Professor; Physiology; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-SEP-1997; Project End 31-MAR-2007 Summary: Abnormal function of salivary gland occurs in radiation, drug therapies, Sjogren's syndrome and Cystic Fibrosis. Saliva is formed by secretion of proteins and

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fluid by acinar cells. The ductal system absorbs the Na+ and Cl- and secretes K+ and HCO3- to form the final saliva. Over the last few years, we came to appreciate the central role of CFTR-regulated HCO3- transport in epithelial fluid and electrolyte secretion, including that by salivary glands. CFTR supports Cl--dependent HCO3transport, and CF-causing mutations with normal C1- channel activity have aberrant HCO3- transport. In the preliminary data we show that SMG express several members of the new SLC26 family of Cl-/HCO3- exchangers-DRA, PDS, SMCBT-and BTR1, that function in HCO3- secretion. SMG also express splice variants on the NBCn1 family that function in HCO3- salvage. The proteins of both families are regulated by CFTR. Based on these findings, we developed a new hypothesis to propose that transcellular HCO3transport is central to salivary gland function and that CFTR coordinates HCO3transport at rest and during stimulation. The hypothesis will be tested by following four aims. In aim 1 we will study the reciprocal regulatory interaction between CFTR and mDRA. Preliminary data shows that CFTR markedly stimulates mDRA activity and that mDRA may affect anion selectivity of CFTR. We will use several CFTR and DRA mutants to a) characterize the mechanism by which CFTR activates mDRA b) study how mDRA affects CFTR channel properties and c) study the reciprocal regulation in vivo in WT and deltaF mice. In aim 2 we will probe interactions between CFTR and the SLC6 family members Pendrin and SLC26A6 that are expressed at high levels in SMG ducts. After basic characterization of SLC26A6 C1-/HCO3- exchange activity, we will probe whether CFTR regulates PDS and SMCBT in vitro and in vivo as it controls mDRA. In aim 3 we will study the role of BTR1 in SMG function. BTR1 is the first member of a new family of HCO3- transporters that is expressed in SMG duct and acinar cells. We propose to characterize Cl- and HCO3- transport by BTR1 as the potential HCO3transporter or channel in the LM of the SMG that generates the final 140 mM HCO3- in saliva. In aim 4 we will characterize regulation of the NBCn1 splice variants by CFTR and their role in HCO3- salvage by the SMG. We will characterize the activity of individual and combinations of NBCn1 isoforms and the mechanism of their inhibition by CFTR in vitro and in vivo using the deltaF mouse. Successful completion of the experiments should considerably clarify the role of CFTR in regulating HCO3homeostasis in the resting and stimulated states. The studies may also shift the emphasis from efforts to correct Cl- transport to efforts to correct Cl- and HCO3transport in diseases of secretory epithelia such as CF and Sjogren's syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR PROGRAMMING OF SALIVARY GLAND GENE EXPRESSION Principal Investigator & Institution: Ann, David K.; Professor; Molecular Pharm & Toxicology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2003; Project Start 01-SEP-1993; Project End 31-JUL-2008 Summary: (provided by applicant): The proposed study intends to elucidate the nuclear events and their subsequent downstream molecular hierarchies that integrate multiple extracellular signaling cascades governing salivary epithelial cell differentiation and proliferation. Our current studies on the characterization of salivary alpha-ENaC expression have led to the identification of a novel cross-talk between Ras/ERK and GR/STAT3 signaling pathways. We demonstrated that the induction of HMGI-C is required to effectively repress GR/Dex-stimulated transcription of alpha-ENaC and to potentiate anchorage-independent cell growth by the Ras/ERK pathway in salivary Pa-4 cells. This Ras/ERK-mediated HMGI-C induction also leads to the formation of an

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HMGI-C/PIAS3 complex which functions as an "off-switch" for attenuating both GR/Dex- and STAT3-mediated transcriptional activation. In this application, we will test the central hypothesis that the spatially and temporally regulated HMGI-C expression plays an essential role in fine-tuning alpha-ENaC expression by antagonizing GR/Dex-mediated trans-activation via formation of the HMGI-C/PIAS3 complex. We will also test the hypothesis that HMGI-C functions as a global gene modulatory factor in vivo by participating in the enhanceosome/repressosome formation, leading to the subsequent phenotypic manifestations in salivary epithelium. The proposed study is of great significance as the perturbation of multiple stimulatory and inhibitory signals and its net outcome are associated with the development of many human systematic or organ-specific diseases, such as Sjogren's syndrome and cancer. Experimentally, there are three Specific Aims in this application: i) to examine functional interactions between HMGI-C and other components of the GR-mediated trans-activation pathway that regulates alpha-ENaC expression in epithelial cells; ii) to perform a comprehensive analysis of alpha-ENaC expression and ENaC function in salivary glands derived from AQP5-HA-HMGI-C transgenic mice; and iii) to determine the potential involvement of HMGI-C in salivary homeostatic regulation. A comprehensive cell biological, molecular biological, biochemical and pharmacological studies are proposed to explore the (patho) physiological consequences of HMGI-C expression in vivo and in vitro. These results will provide us with a blueprint for the "plasticity" of salivary epithelial cell differentiation and proliferation. A better understanding of the functional role for HMGI-C expression could lead to the development of novel therapies that act on critical elements of the signaling pathways governing salivary homeostatic regulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR REGULATION OF LACRIMAL GLAND BRANCHING Principal Investigator & Institution: Lang, Richard A.; Associate Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 452293039 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): The condition of "dry eye" results from diminished production of the aqueous tear component. Some forms of dry eye are age-related and more common in females. Other manifestations of dry eye are associated with inflammatory disorders such as rheumatoid arthritis and Sjogren's syndrome. In rare cases there is a congenital absence of the lacrimal gland. Regardless of the etiology, in severe cases the absence of lubrication to the cornea can result in ulceration and blindness. The frequency of occurrence of dry eye means that it is a significant public health problem. Despite our long-standing knowledge of the dry eye condition and its potentially severe consequences, study of lacrimal gland development using techniques of modern molecular genetics has only recently been initiated. These studies took advantage of a transgene reporter that marked the epithelial component of the gland and allowed us to easily follow the process of budding and branching that occurs during development of the gland. Ultimately, this work showed that both the transcription factor Pax6 (expressed in gland epithelium) and the growth factor FGF10 (expressed in periorbital mesenchyme) were required for normal lacrimal gland development. With the current proposal, it is our intention to build on these studies and examine the role of the transcription factor Barx2, the bone morphogenetic proteins 4 and 7 and the adhesion molecule Ng-CAM in gland morphogenesis. The Specific Aims include (1) an examination of whether an FGF1O gradient is a controlling factor in gland morphogenesis, (2) a determination of how BMPs 4 and 7 can influence lacrimal gland morphogenesis, (3) loss-of-function experiments to determine whether the transcription

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factor Barx2 is required for gland morphogenesis, (4) an assessment of whether there is a regulatory relationship between Barx2 and the BMPs, and (5) a determination of whether Barx2 regulates the expression of the adhesion molecule LI. Combined, these will provide a focussed effort designed to answer questions central to the mechanism of lacrimal gland development and may provide an understanding of how to approach treatment of the dry eye condition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MUCINS OF THE OCULAR SURFACE Principal Investigator & Institution: Gipson, Ilene K.; Senior Scientist; Schepens Eye Research Institute Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-AUG-1979; Project End 31-JUL-2005 Summary: The mucus of the tear film is responsible for maintenance of fluid on the surface of the eye and for providing a microbe barrier to protect the eye from infection. Ocular surface diseases such as those of the dry eye type, vitamin A deficiency, ocular surface infections as well as allergic conjunctivits may involve mucus deficiency, disruption of the mucus layer, or discharge of large amounts of mucus. During the previous funding period, we demonstrated that three mucin genes are expressed by the ocular surface epithelium, two prevalent ones being the membrane- spanning mucin MUC4 and the goblet cell-specific mucin MUC5AC. We sequenced portions of MUC4 and developed probes, antibodies, and assay methods for both mucins that we now propose to use in four specific aims toward understanding aspects of the function and regulation of expression of these mucins on the ocular surface in normal and pathologic states. Aim I: Characterize two aspects of the membrane-spanning mucin MUC4 on the ocular surface. A. determine whether the mucin remains associated with the apical membrane glycocalyx or whether its extracellular domain is shed into the tear film. b. Test candidate inducers of MUC4 gene expression, based on presence of putative transcription factor binding sites identified from sequencing the MUC4 regulatory region and on preliminary data indicating their potential role in its regulation. Aim II: We hypothesize that conjunctival goblet cell differentiation is characterized by induction of expression of the MUC5AC gene and that such induction can be regulated by environmental stimuli as well as cellular effectors. We propose to: a. determine in a mouse model whether goblet cell differentiation/Muc5AC expression can be influenced by surface irritants, infections, or specific allergens; b. determine whether conjunctival goblet cell differentiation can be enhanced in vitro, based on demonstrated presence of regulatory elements in the promoter region of MUC5AC and on culture conditions known to affect gastrointestinal goblet cell differentiation. Aim III: Determine if MUC5AC has specific affinities for MUC4 and the bactericidal proteins prevalent in the tear film, lysozyme, and secretory IgA. Aim IV: Determine in a specific type of dry eye (Sjogren's syndrome), and in seasonal allergic conjunctivitis whether amounts of MUC4 and MUC5AC mRNA and protein differ from the normal population. We hypothesize that dry eye syndromes are characterized by loss of surface wetting due to reduced amounts of MUC5AC and MUC4 protein, whereas, allergic conjunctivitis is characterized by an increased amount of mucins to facilitate allergen removal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NOVEL PROTEINS ASSOCIATED WITH SS-A/RO IN TARGET ORGANS Principal Investigator & Institution: Chan, Edward K.; Professor; Scripps Research Institute Tpc7 La Jolla, Ca 92037

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Timing: Fiscal Year 2002; Project Start 01-MAR-2001; Project End 31-AUG-2002 Summary: (Verbatim) Autoantibody reactivity with the SS-AIRo antigen is an important clinical serological marker for SLE, Sjogren's syndrome, subacute cutaneous lupus erythematosus and neonatal lupus erythematosus (NLE). Two cellular proteins, 60 and 52kDa, have been identified as the predominant targets of the autoimmune response. The long-term objectives of the current proposal are to understand both the origin of this specific autoreactivity and the cellular function of the cognate antigens. Such knowledge should provide critical insights into the pathogenesis of the associated diseases that may differ for each clinical phenotype. Recently a novel 75kDa phosphoprotein (pp75) has been identified as an interaction partner for the 6OkDa SSAIRo protein. In addition it has been identified as an autoantigen recognized by antibodies in sera from patients with Sjogren's syndrome and mothers of children with NLE. Accordingly, three Specific Aims are designed to examine the overall significance of SS-AIRo autoantibodies in the four disease entities and to evaluate if any candidate protein partner(s) of SS-AIRo may provide new clues to the autoimmune pathogenesis. Aim 1 will focus on the identification of pp75 and further define its relationship with 6OkDa SS-A/Ro. Additional experiments will examine whether pp75 is associated with additional proteins. Aim 2 will explore the association of SS-AJRo antigens with other tissue-specific and ubiquitously expressed proteins in the skin, heart, and salivary glands using yeast two-hybrid screen with respective cDNA libraries. The rationale is that each of the target organs may have unique proteins which are available to interact with SS-A/Ro proteins. Differences and similarities among interactions defined in the three affected organs should be highly informative. Aim 3 will address the prevalence of anti-pp75 and antibodies to other putative tissue-specific candidate interaction partners in sera from the four disease groups. Clinical correlations will strengthen the relationship of the antibodies to the pathogenesis of tissue injury. The proposed studies will significantly advance our current understanding of the SS-AIRo antigen/antibody system and its functional role in disease states which target specific organs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OCULAR IMMUNOPATHOLOGY IN AUTOIMMUNE MODELS Principal Investigator & Institution: Jabs, Douglas A.; Professor; Ophthalmology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-AUG-1986; Project End 30-JUN-2004 Summary: Dry eye syndromes are among the most common causes of ocular morbidity in the developed world. Sjogren's syndrome is an autoimmune disorder in which lacrimal gland damage results from a mononuclear inflammatory infiltrate. MRL/Mp1pr/1pr (MRL/1pr) and MRL/Mp-+/+ (MRL/+) mice are congenic murine models of autoimmunity, develop lacrimal gland inflammatory lesions, and are a model for Sjogren's syndrome. The 1pr mutation produces defective Fas antigen, which results in defective lymphocytic apoptosis and accelerates the autoimmune disease. Although the target organ inflammatory lesions in MRL/1pr mice are composed primarily of CD4+ T cells, lymphocyte subset depletion experiments have demonstrated that the lacrimal gland disease can be mediated by either CD4+ T cells or CD8+ T cells. Our investigations will address the mechanisms by which autoimmune lacrimal gland damage occurs in these mice. We hypothesize that the autoimmune lacrimal gland disease in MR/1pr mice; and (4) to intervene therapeutically in vivo and MRL/+ mice is initially an IL-12 driven, Th1-mediated process, which evolves to an IL-2 independent, Th2-mediated process. We also hypothesize that although the lacrimal gland disease is intrinsic to the MRL/Mp strain, the accelerated lacrimal gland disease in MRL/1pr mice

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compared to MRL/+ mice is due to a failure of lymphocytic apoptosis in the lacrimal gland in MRL/1pr mice. The specific aims are: 1) to determine the cytokines present in the lacrimal gland lesions in MRL/1pr and MRL/+ mice and define whether the disease is primarily a Th1- or Th2-mediated disorder and whether there is a change over time; 2) to evaluate the role of the IL-2/IL-2R autocrine pathway in the lacrimal gland disease in MRL/1pr mice, particularly in regard to the time period when this pathway is critical in the establishment of disease; 3) to investigate the pathogenesis of the lacrimal gland disease in MRL/+ mice and the role played by the defective Fas antigen and apoptosis in the accelerated lacrimal gland disease in MRL/1pr mice; and 4) to intervene therapeutically in vivo with monoclonal antibodies to cytokines to define the pathways involved in disease production. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: P2 NUCLEOTIDE RECEPTORS AND SALIVARY GLAND FUNCTION Principal Investigator & Institution: Weisman, Gary A.; Professor; Medical Pharmacology and Physiology; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2003; Project Start 01-AUG-1992; Project End 31-MAY-2008 Summary: (provided by applicant): The overall hypothesis guiding the proposed studies is based on observations that the expression and activity of the P2 nucleotide receptor subtypes in salivary glands change in response to tissue damage, including exocrine disease states, and during development. We posit that these changes are regulated through pathways involving mitogen-activated protein kinases (MAPK) and result in altered expression of P2 receptors that participate in regulating secretion and gene expression. In addition, we posit that the P2Y receptor subtypes found in salivary glands dimerize and that dimerization is an essential aspect of the pharmacological and signaling properties of these receptors. Specific Aim 1 will determine the intracellular signaling pathways involved in regulating P2Y2 receptor expression, with a focus on the mitogen-activated protein kinase cascades. Furthermore, preliminary evidence indicates that up-regulation of P2Y2 receptors coincides with submandibular gland (SMG) dysfunction in a mouse model of Sjogren's syndrome. We propose to evaluate the ability of P2Y2 receptor agonists to enhance secretion in the affected glands as an initial assessment of the receptor as a potential therapeutic target. Specific Aim 2 is to define the consequences of activation of the P2Y2 receptor following up-regulation, focusing on delineation of the signaling pathways utilized by the receptor to modulate secretion and gene expression. Specific Aim 3 will determine if P2Y2 and P2Y1 receptors form homoand hetero-dimers and how dimer formation contributes to receptor function in nonpolarized and polarized model cell systems and in salivary gland cells. Specific Aim 4 is based on observations that P2Y1 receptor activity is high in newborn rat SMG and declines as the gland matures, whereas receptor mRNA levels do not change. This Aim will identify the point(s) in the signaling pathway responsible for the loss of P2Y1 receptor function during SMG development. These studies will initially emphasize prototypical P2 receptor subtypes in the rat and mouse submandibular gland, then will be expanded to address these issues as they relate to the known salivary gland P2 subtypes (P2Y1, P2Y2, P2X4, P2Xy) and to the parotid and sublingual glands, thereby establishing a relatively complete picture of P2 receptor expression and activity in salivary glands under various conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PARTITIONING OF GOLGI MEMBRANES DURING MITOSIS Principal Investigator & Institution: Warren, Graham B.; Professor; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2003; Project Start 10-MAR-2003; Project End 31-DEC-2007 Summary: Accurate partitioning mechanisms ensure the propagation of organelles through subsequent generations. They may also help determine the developmental fate of different daughters. Errors might not only lead to developmental defects but also tumorigenesis. Though the mechanisms underlying chromosomal segregation are well advanced, much less is known about the partitioning of other cellular organelles. This is particularly true for membrane-bound organelles, especially the Golgi apparatus, the focus of this application. Two models have been put forward to explain the partitioning of this organelle. The first argues that the Golgi membranes themselves mediate partitioning, fragmenting at the onset of mitosis, and reassembling in each daughter cell during telophase. The second model argues that the endoplasmic reticulum mediates partitioning, the Golgi merging with it during mitosis and emerging once partitioning of the endoplasmic reticulum is complete. Our data continue to favor the first model but there are unresolved differences between workers concerning the mechanism of Golgi enzyme partitioning. In an effort to resolve these differences and to provide more insight into Golgi partitioning, we shall introduce several new microscopic techniques that will provide a higher resolution view of this process. In addition, one of these techniques involves biotinylation of golgin-84, a new member of the golgin family of Golgi structural proteins that we think is involved in Golgi biogenesis and partitioning. Golgin-84 was discovered as the binding partner of a synaptojanin homologue implicated in oculocerebrorenal syndrome. Since other golgin family members were identified as antigens in the auto-immune disease, Sjogren's syndrome, the hope is that studying these Golgi structural proteins will also shed light on these syndromes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PATHOGENESIS OF CONJUNCTIVAL SQUAMOUS Principal Investigator & Institution: Pflugfelder, Stephen Carl.; Professor; Ophthalmology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-AUG-1997; Project End 31-MAR-2006 Summary: (provided by applicant): Our research has identified that changes in the ocular surface environment of dry eye, such as a hyperosmolar tear film, stimulate the production of pro-inflammatory cytokines by the ocular surface epithelia. Our preliminary data suggests that these cytokines, particularly interleukin-1 (IL-1) and TNF-alpha, may play a key role in the pathogenesis of the epithelial and immunopathology of keratoconjunctivitis sicca, (KCS) the ocular surface disease of dry eye. Four proposed Specific Aims will test this theory. Aim I will confirm whether experimentally induced dry eye in mice stimulates the production and release of proinflammatory cytokines by the ocular surface epithelium that promote ocular surface inflammation and KCS. Aim 2 will determine whether hyperosmolar stress stimulates the production of pro-inflammatory cytokines by the ocular surface epithelium by activating the p38 stress activated protein kinase pathway. Aim 3 will study the expression of IL-1 and TNF-alpha receptors on the ocular surface and determine if there are differences in the expression of these receptors and their soluble antagonists between normal and dry eyes. Aim 4 will investigate the effects of the pro-inflammatory cytokines of dry eye on the expression of matrix metalloproteinase enzymes (MMPs) and mucins on the ocular surface. These factors that have been implicated in the

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disruption of ocular surface barrier function and homeostasis in KCS. These studies will provide clinically relevant information regarding the role of inflammation and its cytokine mediators on the pathogenesis of the ocular surface disease of dry eye, a condition experienced by over 10 percent of the population over the age of 30. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PILOT STUDY--IL 6 GENOTYPES & FRAGILITY RISK IN ELDERLY Principal Investigator & Institution: Walston, Jeremy D.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The purpose of this study is to identify single or combinations of IL-6 gene variants that associate with elevations of serum IL-6 in the Women's Health and Aging I and II cohorts, and to determine the relationship between these genotypes, skeletal muscle strength, and the syndrome of frailty in the same group. The long term goal of this pilot study is to identify clinically relevant IL-6 variants and translate them into test that will identify those older adults at highest risk for losing independence through the development of frailty or its components. Another long-term goal is to develop further studies in order to determine if these clinically relevant gene variants can be markers for those at highest risk for disease complications and poor outcomes. IL-6 mediated chronic inflammation plays a role in the development of frailty in older adults through its contribution to the development of muscle mass and strength decline, glucose intolerance, and anemia. The etiology of this increase in some older adults and not others is multifactorial and includes increased prevalence of acute and chronic disease, declines in sex steroids, and genetic variation. Several specific IL6 gene polymorphisms correlate with increased serum IL-6 and worse outcomes in several inflammatory disease states including rheumatoid arthritis, multiple sclerosis, and Sjogren's syndrome. We hypothesize that specific IL-6 gene variants, individually or in combinations, contribute to higher levels of serum IL-6 in older adults. In order to test this hypothesis, we will genotype consented WHAS 1 and 2 participants for 5 IL-6 single nucleotide polymorphic variants, determine the association between the IL-6 single and combined gene variants and previously measured baseline visit serum IL-6 in the same cohort, and then determine the relationship between these alleles and skeletal muscle strength and with frailty using the expertise and experience of both the Genetics Research Core and the Biostatistics Research Core. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PKC REGULATION OF SALIVARY ACINAR CELL APOPTOSIS Principal Investigator & Institution: Reyland, Mary E.; Associate Professor; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002 Summary: An increase or decrease in apoptosis is likely to contribute to the pathology of a wide range of disorders including those associated with development, autoimmune disease and cancer. In the salivary gland, disorders of apoptosis are likely to contribute to the genesis of salivary gland tumors, as well as Sjogren's syndrome, and autoimmune disorder. In addition, the apoptosis of normal salivary cells in patients treated with head and neck irradiation or chemotherapeutics can result in reduced salivary gland function, or xerostomia. Understanding the mechanisms which regulate apoptosis may suggest avenues for the development of novel therapeutics directed at either enhancing or suppressing apoptosis. The protein kinase C (PKC) family of

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signaling molecules consists of 11 isoforms some of which are thought to play specific roles cell proliferation and cell death. The long-term goal of this proposal is to understand how PKC modulates salivary gland acinar cell apoptosis. The studies described here will use cultures of primary salivary acinar cells, as well as two well differentiated salivary acinar cell lines from the rat parotid and sub-mandibular gland, to explore the hypothesis that activation of specific isoforms of PKC can promote or suppress apoptosis in response to chemotherapeutic drugs, X-irradiation and FAS ligand. Our preliminary results have identified candidate pro-apoptotic (PKCdelta and PKCalpha) PKC isoforms in salivary acinar cells. In AIM 1 we will determine if PKCalpha, PKCbeta1, and/or PKCdelta are activated in primary salivary cells undergoing apoptosis. We will use dominant negative mutants of PKCalpha and PKCdelta to ask if activation of these isoforms is essential for apoptosis. The studies in AIM 2 will focus on understanding how PKCdelta is activated during apoptosis. In AIM 3 we will ask how pro-apoptotic PKC isoforms promote apoptosis by characterizing molecules which function upstream and downstream of PKC in the apoptotic pathway. In addition to the specific application of these studies to salivary acinar cells, this model represents an alternative system in which to study the molecular mechanisms of epithelial cell apoptosis. Thus the information derived from these studies may also have important implications for the development of therapies directed against other epithelial derived tumors such as those of the breast and pancreas. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROLACTIN AS A LACRIMAL GLAND IMMUNOREGULATOR Principal Investigator & Institution: Schechter, Joel E.; Cell & Neurobiology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2003; Project Start 01-APR-1994; Project End 31-DEC-2006 Summary: (provided by applicant): Dry eye is one of the most frequently encountered problems in ophthalmology, with highest incidence in women, especially postmenopausally where atrophy and decreased tear formation are associated with chronic inflammation. It also occurs in Sjogren's syndrome, an autoimmune disease characterized by lymphocytic infiltration and loss of lacrimal acinar cells. The hormonal milieu is a critical factor in maintenance of normal lacrimal function, and androgens and prolactin (PRL) both play important roles. We have demonstrated that lacrimal fluid production in rabbits is decreased during pregnancy, and that pregnant women experience increased symptoms of dry eye, worsening with multiple pregnancies. Our studies in rabbits demonstrate dramatic changes in the concentration and distribution of PRL and growth factors within the lacrimal gland (LG) during pregnancy and lactation, increasingly being concentrated within ductal epithelial cells. These changes are accompanied by the appearance of "reactive acinar cells," which are immunopositive for MHC Class II protein and which may also be passive sources of autoantigenic stimulation, and by a marked redistribution of T and B lymphocytes from their normal periductal location to interacinar sites. We propose a new paradigm for physiological regulation of LG function, i.e., an "acinar-ductal loop." In this system, ductal epithelial cells monitor the contents of the acinar effluent, absorb and transport materials from the duct lumen to periductal immune cells, and in so doing function in transmitting immunoregulatory signals (PRL, growth factors, cytokines) that may enhance periductal immune cell activation and responses to autoantigens. We propose to approach this integrated physiological system from perspectives of endocrinology and cellular physiology, employing rabbits, and mouse models of Sjogren's syndrome to pursue the following specific aims: (1) Test the hypothesis that lacrimal acinar cells and lacrimal

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ductal epithelial cells represent a physiological loop, in which ductal epithelial cells monitor acinar fluid contents, absorb and transport materials from within the duct lumen, and function in local immunoregulation. (2) Test the hypothesis that artificially altering the hormonal milieu of non-pregnant rabbits will elicit responses in the LG which are identical to those observed during pregnancy and lactation. (3) Use in vitro methods to characterize the effects of pregnancy, and growth factors whose expression is increased during pregnancy, on secretory function and intracellular autoantigen traffic in lacrimal acinar cells. (4) Test the hypothesis that increased PRL, charactersitic of pregnancy and lactation, enhances activation of lymphocytes in the LG. (5) Test the hypothesis that pregnancy accelerates and exacerbates the progress of Sjogren's-like infiltration of the LG in mouse models of Sjogren's syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF THE IMMUNE RESPONSE IN SJOGRENS SYNDROME Principal Investigator & Institution: Fox, Robert I.; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RETROVIRAL ETIOLOGY OF PRIMARY BILIARY CIRRHOSIS Principal Investigator & Institution: Mason, Andrew L.; Associate Professor; Ochsner Clinic Foundation New Orleans, La 70121 Timing: Fiscal Year 2002; Project Start 30-SEP-1997; Project End 31-JUL-2002 Summary: Primary biliary cirrhosis (PBC) is an idiopathic multisystem autoimmune disorder that primarily effects women. Patients with PBC have a pluriglandular syndrome resulting in cirrhosis and sicca syndrome, and a demonstrable autoimmune response to specific mitochondrial oxo-acid dehydrogenase E2 proteins. PBC patients are also prone to develop other autoimmune diseases such as Sjogren's syndrome, thyroiditis, and systemic lupus erythematosus. These autoimmune disorders have all been linked to rettroviral infection as by Western blot studies 30 to 35 percent of patients have indeterminate serum reactivity to HIV proteins and 85 to 05 percent have serum reactivity to human intracisternal A type particle (HIAP-I) which was isolated from salivary glands of patients with Sjogren's syndrome and also visualized by electron microscopy. Likewise, 15 percent of PBC patients have been reported to have false positive HIV ELISA reactivity and in preliminary studies, retrovirus particles have been observed by electron microscopy in the biliary epithelial cells of PBC patients but not controls. Using representational difference analysis, we have isolated and cloned novel retroviral nucleic acid sequences from the liver of a PBC patients. These clones have been used to screen a cDNA library made from bilary epithelium cells isolated from three transplant recipients with PBC. We have now identified more than ten qunique cDNA clones with sequence homology to HIV, SIV, HTLV-1, and IAP as well as the E2 mitochondrial autoantigens. To date, our RTPCR studies have revealed that all the RDA and 3 of 3 novel clones tested to data are not unique to PBC patients, suggesting that they may be derived from endogenous retroviruses. Also, we have conducted Western blot studies which reveal that approximately 74 percent of PBC patients sera have indeterminate reactivity to HIAP proteins and 35 percent of patients react to HIV p24 gag, compared to less than 5 percent of liver disease controls. This suggests that the

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putative PBC retrovirus shares antigenic determinants with HIV-I and HIAP-I but is a separate virus. In order to further characterize the agent associated with PBC, we plan to identify specific retroviral proteins and nucleic sequences with the ultimate goal of investigating the role this virus plays in the eitology of PBC. Our specific aims are to (1) Clone full length PBC retrovirus from hepatic tissue and PBC cDNA libraries; (2) Isolate the PBC retrovirus in lymphoblastoid and hepatic cell lines by co-culture with infected hepatic tissue; (3) Assess the prevalence of retroviral infection in PBC patients and controls by nucleic acid hybridization techniques and western blot experiments of recombinant or purified viral proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF AQUAPORIN (AQP) 5 IN SALIVARY SECRETION Principal Investigator & Institution: Menon, Anil G.; Associate Professor; Molecular Genetics, Biochemistry & Microbiology; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-JUL-2005 Summary: (Adapted from the Investigator's Abstract): Saliva formation depends on the coordinated action of multiple processes involving the regulation of paracellular junctions as well as precise regulation of ion and water transporters in the acinar and ductal cells of the salivary gland. Ion fluxes across the apical membrane in acinar cells are thought to generate an osmotic gradient that drives paracellular water transport while creating an isotonic primary secretion. The lack of proper salivary secretion results in dry mouth, which may be idiopathic or associated with disorders such as Sjogren's syndrome. A significant number of individuals in the older population also suffer from medication-induced dry mouth in the US. Recent evidence suggests that water is transported in salivary acinar cells via a transcellular route through water channels, or aquaporins (AQPs). At least four AQPs are expressed in salivary glands. These include AQP1 (capillary endothelium), AQP4 (basolateral membrane of ductal cells), AQP5 (apical membrane of acinar cells) and AQP8 (cellular distribution unknown). Direct evidence in support of a role for AQP5 in fluid secretion in the salivary gland has been demonstrated in Aqp5 null mice, which secrete low volume hypertonic viscous saliva in response to supra-maximal muscarinic stimulation (Ma et al, 1999). This evidence suggests that transepithelial transport through water channels provides an important route for water flow through salivary secretion, and that the AQP5 water channel plays a major role in the process. The identification of aberrant salivary secretion in the AQP5 null mice is therefore the first direct evidence for requiring AQP5 in normal salivary secretion. The tasks ahead are to understand the regulatory, functional and physiological roles played byAQP5 in saliva secretion, which remains unknown at this time. In this proposal, plans are put forth to use a combination of cell biological, physiological and genomic approaches to analyze a mouse in which the AQP5 gene has been "knocked out" by gene targeting in order to elucidate the role, and to identify the mechanisms, by which AQP5 regulates the formation of saliva. This multidisciplinary approach will refine current understanding of the water transport mechanisms involved in the production of saliva, and provide valuable information on targets for the development of treatments for salivary gland dysfunction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF SMALL GTPASES IN MUSCARINIC RECEPTOR TRAFFICKING Principal Investigator & Institution: Radhakrishna, Harish; None; Georgia Institute of Technology 505 Tenth St. Nw Atlanta, Ga 303320420 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2005 Summary: This is a proposal to investigate the cellular mechanisms that regulate the extent of signaling by the Gi- coupled m2 muscarinic acetylcholine receptors (m2Rs). These important regulators of cardiovascular function counteract the effects of adrenaline to either stimulate myopulmonary contraction or to decrease the rate and force of myocardial contraction. Limiting m2R signaling is critical for normal cardiac function since persistent activation (e.g., Sjogren's syndrome) often leads to congestive heart failure. One key mechanism that contributes to limiting m2R activity is receptor endocytosis. Although much is known about the mechanisms leading to m2R internalization (e.g., m2R phosphorylation) very little is known about how the subsequent post-endocytic trafficking of m2Rs is regulated. Members of the ARF and Rab families of GTPases are known to regulate the compartment-to-compartment trafficking of nutrient receptors like those that bind LDL or transferrin. In contrast, nothing is known about the role of these GTPases in regulating the intracellular trafficking and function of any muscarinic receptor class. Our recent observations suggest that the ARF6 GTPase, which regulates a non-clathrin mediated endocytic pathway, may regulate the trafficking of m2Rs, which are also internalized via an illdefined, non-clathrin dependent mechanism. These preliminary results provide support for the CENTRAL HYPOTHESIS of this proposal that specific ARF (ARF6) and Rab (Rabs 5 and 7) regulate the intracellular trafficking and sorting of internalized m2Rs. TO TEST THIS HYPOTHESIS, we will use a combination of molecular, morphological, and biochemical approaches to focus on the following THREE SPECIFIC AIMS. FIRST, we will define the post-endocytic itinerary of internalized m2Rs in cells. SECOND, we will determine the role of specific ARF(6) and Rab(5,7) GTPases in regulating multiple aspects of m2R trafficking. THIRD, we will investigate the role of these GTPases in regulating m2R-mediated ERK2 activation. The information gathered by this proposal will provide new information about the regulation of post-endocytic m2R trafficking and will lend insight into the relationship between ARF6-regulated and clathrindependent endocytic trafficking. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF THE BCL-2 AND CASPASE FAMILY IN ACINAR APOPTOSIS Principal Investigator & Institution: Quissell, David O.; Professor & Chairman; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002 Summary: Salivary gland hypofunction is a major oral health problem that affects the quality of life for several million people in the USA. A variety of conditions can resulting in the loss of salivary acinar cell secretory function including systemic diseases such as Sjogren's Syndrome (an autoimmune disease), X-ray irradiation, cancer chemotherapy, psychological factors, malnutrition, pharmacological induced xerostomia and oral cancer. All of these disease conditions or treatments have the potential to alter normal salivary acinar cell homeostasis and to accelerate the entry of the salivary gland acinar cells into apoptosis. A fundamental understanding of the molecular events

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involved in salivary gland acinar apoptosis is required if we are to fully comprehend the specific mechanisms involved in salivary gland hypofunction. This information is also essential for the development of new treatment modalities that have the potential to block or delay the toxic effects of these various disease conditions and treatments on normal acinar cell function. The principle objective of this project is to investigate and determine at the molecular level the precise function of the two major cellular protein families that play a central role in the initiation signaling and execution of acinar cell apoptosis. The two critical regulatory protein families are the caspase and the Bcl-2 family of proteins. We will determine their level of expression, subcellular distribution, level of phosphorylation and their functional activity during t he onset and duration of acinar cell apoptosis elicited by specific apoptotic stimuli. These studies will be performed using primary cultures of rat parotid and sub-mandibular acinar cells and immortalized rat parotid and sub-mandibular acinar cell lines. The identification and characterization of these two critically important protein families will provide new basic scientific information and insights for the development of new therapeutic approaches to suppress aberrant acinar cell apoptosis, with the long term objective to improve the quality of life for millions of affected individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SALIVA & ANTI CANDIDAL DEFENSE MECHANISMS IN HIV & AIDS Principal Investigator & Institution: Yeh, Chih-Ko; Associate Professor; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: This study is based on the hypotheses that: 1) alterations in salivary gland function are associated with the progression of HIV infection and these alterations predispose to oral candidiasis; 2) with increasing severity of HIV infection, patients develop Sjogren's Syndrome-like features. The study will cross-sectionally and longitudinally determine salivary gland changes at the different stages of HIV infection, it will determine the changes in salivary anti-candidal activities with the progression of HIV infection, and will determine the similarities and differences in salivary gland function of HIV-infected patients in comparison to those with Sjogren's. The study will utilize age- and sex-matched sero-negative controls and patients at different stages of HIV infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SIALOADENITIS IN AG INDUCED AND SPONTANEOUS AUTOIMMUNITY Principal Investigator & Institution: Fu, Shu M.; Professor and Chair; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-JUL-2004 Summary: (adapted from the Investigator's Abstract): This proposal focuses on the pathogenesis of Sjogren's Syndrome (SS), a systematic autoimmune disease largely affecting the exocrine glands. The disease has been defined as the combination of dry eyes and dry mouth due to lymphocytic infiltration of these glands (sialoadenitis). The syndrome is often, if not always, associated with autoantibodies to SSA/Ro and SSB/La. It is a prevalent disorder with considerable ocular and oral morbidity. long term goal of the research program is to elucidate the immunological and genetic factors which are important in the development of sialoadenitis. In this application a murine model of

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sialoadenitis will be defined. Four specific aims are included.Four specific aims are included. In Specific Aim 1, different strains of mice will be identified which are susceptible to the induction of sialoadenitis by immunization with recombinant Ro60, Ro522 or La. Functional, histochemical and immunocytochemical studies will be done to monitor the development of sialoadenitis. In animals with salivary infiltrates, the involvement of other exocrine glands and tissues will be determined. Further studies will identify Ro60 peptides capable of inducing sialoadenitis. Considerable efforts will be devoted to determining whether salivary gland dysfunction is present in mice which have developed antigen induced sialoadenitis in order to validate this model to studying SS. In Specific Aim 2, T cell lines and clones from infiltrating T cells of disease salivary glands and the draining lymph nodes will be generated after stimulation with mouse salivary gland cellular extract. The responsible antigens will be identified and pathogenic potential of the T cell lines determine by cell transfer experiments. Additionally, the T cell specificities of cell lines derived from these mice will be compared with those derived from NOD mice, a model for spontaneous autoimmunity. In Specific Aim 3, the feasibility of developing an autoantigen-induced sialoadenitis in mice expressing certain HLA-DR and/or HLA-DQ transgenes will be explored. By a rapid breeding scheme, these transgenes will be bred into appropriate background for the development of sialoadenitis as determined in Specific Aim 1. In the fourth specific aim, B-less mice which are congenic with the sialoadenitis susceptible strains will be generated to explore the role of B cells in both the spontaneous and antigen-induced autoimmune model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STIMULUS/SECRETION COUPLING IN DISEASED LACRIMAL GLAND Principal Investigator & Institution: Zoukhri, Driss; Schepens Eye Research Institute Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 29-SEP-2003 Summary: Sjogren's syndrome is the leading cause of aqueous tear deficient dry eye. Sjogren's syndrome is an autoimmune disease, which occurs almost exclusively in females (>90%), is associated with extensive lymphocytic accumulation in the lacrimal gland and destruction of epithelial cells resulting in insufficient fluid and protein secretion leading to dry eye. To date there are no treatments or cures for this disease. The long term objective of the present proposal is to determine, using marine models of Sjogren's syndrome, the effect of the lymphocytic accumulation in the lacrimal gland on nerve functionality, intracellular signaling pathways, and protein and fluid secretion. A second objective is to test the role of cytokines, especially interleukin-1beta (IL-1beta), in the impaired function of the lacrimal gland in Sjogren's syndrome, and if IL-1 receptor antagonist (IL-1-ra) treatment can restore lacrimal gland function. To obtain these goals, the following specific aims have been proposed: (1) determine functionality of nerves and neurotransmitters in the lacrimal gland after the onset and during the progression of the lymphocytic accumulation; (2) determine if all signaling pathways are upregulated in the lacrimal gland with the onset and progression of lymphocytic accumulation, and if blocking this accumulation prevents the up-regulation; and (3) determine if protein and fluid secretion induced by neural stimulation of the lacrimal gland of diseased mice is altered. Lacrimal gland slices or acini will be prepared from diseased and control female mice. The release of neurotransmitter from lacrimal gland nerve endings will be measured by HPLC. The amount of IL-1beta will be determined by western blotting and ELISA. The effect of lymphocytic accumulation on lacrimal

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gland signaling pathways will be determined by measuring: (1) changes in [Ca2+], using Ca2+ sensitive probes; (2) changes in [cAMP] using an enzyme immunoassay (EIA) kit, and (3) changes in PKC location using immunofluorescence microscopy. Lacrimal gland secretion will be determined either in vitro, by measuring peroxidase or newly synthesized proteins secretion from acini or lobules, or in vivo by cannulating lacrimal ducts or using the Schirmer test. IL-1-ra will be given s.c. (21-day release pellets) in the capsular region of diseased animals. Serum levels of IL-1-ra will be determined by ELISA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STUDY OF T CELL CHARACTERISTICS AND ADHESION MOLECULES Principal Investigator & Institution: Bergasa, Nora V.; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: Primary biliary cirrhosis (PBC) is chronic liver disease of unknown etiology. Histologically, PBC is characterized by a progressive immunologically mediated inflammation known as chronic nonsuppurative destructive cholangitis (CNSDC) that leads to bile duct destruction, ductopenia and biliary cirrhosis. At present there is no cure for PBC. The most common symptoms associated with PBC are fatigue and pruritus. More than 90% of patients with PBC are women. The average age of diagnosis is about 50 years. Asymptomatic patients have a four-fold increase in mortality when compared to the U.S.A. population matched for age and the median survival from the onset of symptoms is 7.5 to 9 years. PBC is considered a model autoimmune disease; it is associated with hypergammaglobulinemia, autoantibodies, defects of immune regulation, and an increased incidence of other autoimmune conditions (thyroiditis, Sjogren's syndrome, scleroderma). The liver injury is characterized by a rich inflammatory infiltrate composed of CD4+ and CD8+ cells, cytokines, adhesion molecules and other immunologic mediators. The consequence of CNSDC is biliary cirrhosis and liver failure. The only treatment approved to treat PBC is ursodeoxycholic acid (UDCA), which appears to delay the time to liver transplantation but does not cure for the disease. Thus, the need for the provision of effective and safe treatments for PBC is clear. Patients with PBC may benefit from treatment with an appropriate immunosuppressive drug. Mycophenolate mofetil meets the criteria of a superior immunosuppressive agent. In this proposal we are going to explore immune mediators of PBC including T cells and adhesion molecules in patients with PBC and the effect of treatment with MMF in combination with UDCA on these factors in patients who are participants in a clinical trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE QUALITY CONTROL PROTEINS RO AND LA AND RNA FOLDING Principal Investigator & Institution: Reinisch, Karin M.; Cell Biology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): The work proposed here focuses on two chaperonelike proteins that play critical roles in the biogenesis of small RNAs. The 60kDa Ro protein is part of a quality control system for small RNAs; it recognizes misfolded variant pre-5S rRNAs and U2 RNAs and targets them for degradation. Ro protects the

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cell against UV damage, and its proper function is necessary to protect against autoimmune disorders. The ~50kDa La is the first protein to associate with many RNA polymerase III transcripts immediately after their synthesis and facilitates their correct maturation and targeting. Additionally, it has been shown to assist in the correct folding of certain pre-tRNAs in vivo. Our first aim is to determine the crystal structure of the Ro protein and to investigate by mutagenesis how it interacts with RNA. Diffraction quality crystals have been obtained in preliminary studies. The second aim is to determine crystal structures of Ro and RNA in order to understand how Ro recognizes misfolded small RNAs and how Ro modulates its affinity for different RNAs. Mutagenesis studies will be used to investigate which protein-RNA interactions are most important in determining the affinity and specificity of Ro for RNAs. The third aim is to determine a crystal structure for the La protein, preferably bound to RNA, as the first step in investigating how La interacts with RNA. All three aims are directed at understanding how proteins interact with RNAs at the atomic level. Additionally, since both Ro and La are major autoantigens for the autoimmune diseases Sjogren's syndrome and systemic lupus erythematosus, their three-dimensional structures may be useful in determining how they trigger an autoimmune response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THYMOSIN BETA 4 AND AUTOIMMUNE OCULAR SURFACE DISEASE Principal Investigator & Institution: Sosne, Gabriel; Anatomy and Cell Biology; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Keratoconjunctitivitis sicca (KCS), or dry eye disease, is one of the most common conditions seen by ophthalmologists and affects 15% of those from 65-84 years of age, or 4.3 million Americans. The pathophysiology of dry eye includes immune-mediated inflammation involving both the ocular surface and the lacrimal gland. While knowledge of the pathology of dry eye disease has improved significantly during recent years, the mainstay of treatment, ocular lubrication, provides only palliative relief at best to patients with severe dry eye disease. Therefore, attention has turned to immunomodulation as a therapeutic approach for I severe dry eye disease, especially for that seen in autoimmune diseases like Sjogren's syndrome, I rheumatoid arthritis, and systemic lupus erythematosus (SLE). Available agents such as corticosteroids have I considerable side effects that render them therapeutically impotent in a number of patients. Recently, the FDA approved Cyclosporine A (CSA), 0.5% (Restasis) for the treatment of moderate to severe dry eye. However, 85% of CSAtreated patients did not experience a significant increase in tear production. Therefore, a therapeutic agent that could reliably decrease immune-mediated ocular surface damage without significant adverse effects in a large proportion of affected patients would constitute a major therapeutic advance, particularly for dry eye disease. Thymosin beta 4 (Tb4) promotes corneal wound healing and reduces inflammation in mice after chemical injury to the eye. Since Tb4 has both anti-inflammatory and wound healing properties, it is an ideal candidate for evaluation in an autoimmune model of dry eye. Two specific aims are proposed to test the overall hypothesis of this application that Tb4 modulates lacrimal gland, corneal and conjunctival inflammation in an animal model of autoimmune dry eye disease. 1) To test the hypothesis that Tb4 alters production of cytokines, chemokines and specific matrix metalloproteinases (MMPs) in a murine model of Sjogren's syndrome; 2) To test the hypothesis that Tb4 alters autoimmune ocular surface damage in the MRL/Ipr mouse by decreasing lacrimal gland

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inflammation and conjunctival squamous metaplasia. By identifying Tb4 as a novel wound healing and anti-inflammatory agent to protect the ocular surface from inflammatory and immune tissue injury, it is aimed to substantiate the potential clinical usage of Tb4 for the majority of patients who are not relieved by currently available therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “Sjogren’s syndrome” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for Sjogren’s syndrome in the PubMed Central database: •

An unusual presentation of Sjogren's syndrome. by Crooks GW, Zweiman B.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170377

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Analysis of immunoglobulin light chain rearrangements in the salivary gland and blood of a patient with Sjogren's syndrome. by Jacobi AM, Hansen A, Kaufmann O, Pruss A, Burmester GR, Lipsky PE, Dorner T.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125296

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Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjogren's syndrome. by Groom J, Kalled SL, Cutler AH, Olson C, Woodcock SA, Schneider P, Tschopp J, Cachero TG, Batten M, Wheway J, Mauri D, Cavill D, Gordon TP, Mackay CR, Mackay F.; 2002 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150825

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Nucleotide sequence of a uniquely expressed human T cell receptor beta chain variable region gene (V beta) in Sjogren's syndrome. by Freimark B, Pickering L, Concannon P, Fox R.; 1989 Jan 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=331575

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Reactivity of Sera from Systemic Lupus Erythematosus and Sjogren's Syndrome Patients with Peptides Derived from Human Immunodeficiency Virus p24 Capsid Antigen. by Deas JE, Liu LG, Thompson JJ, Sander DM, Soble SS, Garry RF, Gallaher WR.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=121355

3 4

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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Sicca Syndrome Associated with Tropheryma whipplei Intestinal Infection. by Bosman C, Boldrini R, Borsetti G, Morelli S, Paglia MG, Visca P.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120622

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The liver is a common non-exocrine target in primary Sjogren's syndrome: A retrospective review. by Kaplan MJ, Ike RW.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128830

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Transfer of human serum IgG to nonobese diabetic Ig[mu]null mice reveals a role for autoantibodies in the loss of secretory function of exocrine tissues in Sjogren's syndrome. by Robinson CP, Brayer J, Yamachika S, Esch TR, Peck AB, Stewart CA, Peen E, Jonsson R, Humphreys-Beher MG.; 1998 Jun 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22675

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with Sjogren’s syndrome, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “Sjogren’s syndrome” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for Sjogren’s syndrome (hyperlinks lead to article summaries): •

A comparison of salivary gland hypofunction in primary and secondary Sjogren's syndrome. Author(s): Dawson LJ, Holt DJ, Higham SM, Longman LP, Field EA. Source: Oral Diseases. 2001 January; 7(1): 28-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11354918

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A new mathematical model based on clinical and laboratory variables for the diagnosis of Sjogren's syndrome. Author(s): Martin-Martin LS, Latini A, Pagano A, Ragno A, Stasi R, Coppe A, Davoli G, Crescenzi A, Alimonti A, Migliore A. Source: Clinical Rheumatology. 2003 May; 22(2): 123-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12740677

6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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•

A rare case of cardiac sarcoidosis in a patient with progressive systemic sclerosis, Sjogren's syndrome, and polymyositis. Author(s): Hosoya N, Mimura T, Enokawa Y, Mizuno T, Hamasaki K, Matsuyama T, Matsuhashi N, Yotsumoto H, Yazaki Y. Source: Intern Med. 1995 December; 34(12): 1164-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8929642

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A technique for minor salivary gland biopsy used in the diagnosis of Sjogren's syndrome. Author(s): Laiho K, Sorsa S. Source: Clinical Rheumatology. 2003 May; 22(2): 164. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12740690

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An unusually complicated case of primary Sjogren's syndrome: development of transient "lupus-type" autoantibodies following silicone implant rejection. Author(s): Asherson RA, Shoenfeld Y, Bosman C. Source: The Journal of Rheumatology. 2004 January; 31(1): 196-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14705243

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Analysis of B-cell clonality in the hepatic tissue of patients with Sjogren's syndrome. Author(s): Tokuno T, Takahashi H, Suzuki C, Yamamoto M, Naishiro Y, Sugaya A, Sakamoto H, Imai K. Source: Scandinavian Journal of Rheumatology. 2003; 32(5): 268-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14690138

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Anti-alpha-fodrin antibodies in Sjogren's syndrome in children. Author(s): Maeno N, Takei S, Imanaka H, Oda H, Yanagi K, Hayashi Y, Miyata K. Source: The Journal of Rheumatology. 2001 April; 28(4): 860-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11327263

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Antibodies against alpha-fodrin in Sjogren's syndrome. Author(s): Ulbricht KU, Schmidt RE, Witte T. Source: Autoimmunity Reviews. 2003 March; 2(2): 109-13. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12848967

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Antibodies raised against the second extracellular loop of the human muscarinic M3 receptor mimic functional autoantibodies in Sjogren's syndrome. Author(s): Cavill D, Waterman SA, Gordon TP. Source: Scandinavian Journal of Immunology. 2004 March; 59(3): 261-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15030576

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Anti-Ro/SSA and anti-La/SSB autoantibodies in the tear fluid of patients with Sjogren's syndrome. Author(s): Toker E, Yavuz S, Direskeneli H. Source: The British Journal of Ophthalmology. 2004 March; 88(3): 384-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14977774

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Aquaporins in primary Sjogren's syndrome: comment on the articles by Steinfeld et al. Author(s): Waterman SA, Beroukas D, Hiscock J, Jonsson R, Gordon TP. Source: Arthritis and Rheumatism. 2003 April; 48(4): 1167-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12687572

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Are women with Sjogren's syndrome androgen-deficient? Author(s): Sullivan DA, Belanger A, Cermak JM, Berube R, Papas AS, Sullivan RM, Yamagami H, Dana MR, Labrie F. Source: The Journal of Rheumatology. 2003 November; 30(11): 2413-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14677186

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Association of transforming growth factor beta1 and tumor necrosis factor alpha polymorphisms with anti-SSB/La antibody secretion in patients with primary Sjogren's syndrome. Author(s): Gottenberg JE, Busson M, Loiseau P, Dourche M, Cohen-Solal J, Lepage V, Charron D, Miceli C, Sibilia J, Mariette X. Source: Arthritis and Rheumatism. 2004 February; 50(2): 570-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14872501

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Association of vitiligo with Sjogren's syndrome. Author(s): Montes LF, Pfister R, Elizalde F, Wilborn W. Source: Acta Dermato-Venereologica. 2003; 83(4): 293. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12926804

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Attenuated apoptosis of B cell activating factor-expressing cells in primary Sjogren's syndrome. Author(s): Szodoray P, Jellestad S, Teague MO, Jonsson R. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2003 March; 83(3): 357-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12649336

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Autoantibodies to alpha-fodrin in primary Sjogren's syndrome and SLE detected by an in vitro transcription and translation assay. Author(s): Nordmark G, Rorsman F, Ronnblom L, Cajander S, Taussig MJ, Kampe O, Winqvist O. Source: Clin Exp Rheumatol. 2003 January-February; 21(1): 49-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12673889

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Autoantibodies to tissue transglutaminase in Sjogren's syndrome and related rheumatic diseases. Author(s): Luft LM, Barr SG, Martin LO, Chan EK, Fritzler MJ. Source: The Journal of Rheumatology. 2003 December; 30(12): 2613-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14719202

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Autoimmune hepatitis concomitant with hypergammaglobulinemic purpura, immune thrombocytopenia, and Sjogren's syndrome. Author(s): Wada M, Kamimoto H, Park SY, Shintani S, Nakasho K. Source: Intern Med. 2001 April; 40(4): 308-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11334390

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Autonomic involvement in Sjogren's syndrome. Author(s): Smith AJ, Waterman SA, Gordon TP. Source: The Journal of Rheumatology. 2003 October; 30(10): 2296; Author Reply 2296-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14528535

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Autonomic nervous system dysfunction involving the gastrointestinal and the urinary tracts in primary Sjogren's syndrome. Author(s): Kovacs L, Papos M, Takacs R, Roka R, Csenke Z, Kovacs A, Varkonyi T, Pajor L, Pavics L, Pokorny G. Source: Clin Exp Rheumatol. 2003 November-December; 21(6): 697-703. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14740447

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B cell clonality in gastric lymphoid tissues of patients with Sjogren's syndrome. Author(s): Ferraccioli GF, Sorrentino D, De Vita S, Casatta L, Labombarda A, Avellini C, Dolcetti R, Di Luca D, Beltrami CA, Boiocchi M, Bartoli E. Source: Annals of the Rheumatic Diseases. 1996 May; 55(5): 311-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8660105

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B-cell lymphoma of mucosa-associated lymphoid tissue of the thymus: a report of two cases with a background of Sjogren's syndrome and monoclonal gammopathy. Author(s): Yamasaki S, Matsushita H, Tanimura S, Nakatani T, Hara S, Endo Y, Hara M. Source: Human Pathology. 1998 September; 29(9): 1021-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9744322

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B-cell lymphoproliferation in primary Sjogren's syndrome. Author(s): Tzioufas AG. Source: Clin Exp Rheumatol. 1996 January-February; 14 Suppl 14: S65-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8722203

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Benefit of IVIg for long-standing ataxic sensory neuronopathy with Sjogren's syndrome. Author(s): Wolfe GI, Nations SP, Burns DK, Herbelin LL, Barohn RJ. Source: Neurology. 2003 September 23; 61(6): 873; Author Reply 873. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14723230

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Benefit of IVIg for long-standing ataxic sensory neuronopathy with Sjogren's syndrome. Author(s): Burns TM, Quijano-Roy S, Jones HR. Source: Neurology. 2003 September 23; 61(6): 873; Author Reply 873. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14504354

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Benefit of IVIG for long-standing ataxic sensory neuronopathy with Sjogren's syndrome. IV immunoglobulin. Author(s): Takahashi Y, Takata T, Hoshino M, Sakurai M, Kanazawa I. Source: Neurology. 2003 February 11; 60(3): 503-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12578938

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Beta 2 microglobulin measurements in saliva of patients with primary Sjogren's syndrome: influence of flow. Author(s): van der Geest SA, Markusse HM, Swaak AJ. Source: Annals of the Rheumatic Diseases. 1993 June; 52(6): 461-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8323400

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Biclonal immunoglobulin M dysglobulinaemia: evolving aspects in a case of primary Sjogren's syndrome. Author(s): Pontet F, Halimi C, Brocard A, Delacour T. Source: Eur J Clin Chem Clin Biochem. 1997 April; 35(4): 287-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9166971

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Big prolactin 60 kDa is overexpressed in salivary glandular epithelial cells from patients with Sjogren's syndrome. Author(s): Steinfeld S, Rommes S, Francois C, Decaestecker C, Maho A, Appelboom T, Heizmann CW, Kiss R, Pochet R. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2000 February; 80(2): 239-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10701693

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Bilateral and multicystic major salivary gland disease: a rare presentation of primary Sjogren's syndrome. Author(s): Ahmad I, Ray J, Cullen RJ, Shortridge RT. Source: The Journal of Laryngology and Otology. 1998 December; 112(12): 1196-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10209623

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Bilateral parotid cysts as presentation of Sjogren's syndrome. Author(s): Plaza G, Dominguez MP, Bueno A. Source: The Journal of Laryngology and Otology. 2003 February; 117(2): 151-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12625896

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Bilateral parotid MALT lymphoma and Sjogren's syndrome. Author(s): Stewart A, Blenkinsopp PT, Henry K. Source: The British Journal of Oral & Maxillofacial Surgery. 1994 October; 32(5): 318-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7999742

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Biochemical deficiency of pyridoxine does not affect interleukin-2 production of lymphocytes from patients with Sjogren's syndrome. Author(s): Tovar AR, Gomez E, Bourges H, Ortiz V, Kraus A, Torres N. Source: European Journal of Clinical Nutrition. 2002 November; 56(11): 1087-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12428174

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Biochemical markers of renal disease in primary Sjogren's syndrome. Author(s): Eriksson P, Denneberg T, Larsson L, Lindstrom F. Source: Scandinavian Journal of Urology and Nephrology. 1995 December; 29(4): 383-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8719354

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Biopsy of labial salivary glands and lacrimal glands in the diagnosis of Sjogren's syndrome. Author(s): Norman JE. Source: The Journal of Rheumatology. 1997 February; 24(2): 409. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9035010

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Biopsy of labial salivary glands and lacrimal glands in the diagnosis of Sjogren's syndrome. Author(s): Xu KP, Katagiri S, Takeuchi T, Tsubota K. Source: The Journal of Rheumatology. 1996 January; 23(1): 76-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8838512

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Bm1-Bm5 classification of peripheral blood B cells reveals circulating germinal center founder cells in healthy individuals and disturbance in the B cell subpopulations in patients with primary Sjogren's syndrome. Author(s): Bohnhorst JO, Bjorgan MB, Thoen JE, Natvig JB, Thompson KM. Source: Journal of Immunology (Baltimore, Md. : 1950). 2001 October 1; 167(7): 3610-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11564773

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Botulinum toxin increases tearing in patients with Sjogren's syndrome: a preliminary report. Author(s): Spiera H, Asbell PA, Simpson DM. Source: The Journal of Rheumatology. 1997 September; 24(9): 1842-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9292815

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Brief report: a single neoplastic clone in sequential biopsy specimens from a patient with primary gastric-mucosa-associated lymphoid-tissue lymphoma and Sjogren's syndrome. Author(s): Diss TC, Peng H, Wotherspoon AC, Pan L, Speight PM, Isaacson PG. Source: The New England Journal of Medicine. 1993 July 15; 329(3): 172-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8515789

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Bronchial hyperreactivity in systemic sclerosis patients: influence of associated Sjogren's syndrome. Author(s): La Corte R, Bajocchi G, Potena A, Govoni M, Trotta F. Source: Annals of the Rheumatic Diseases. 1995 August; 54(8): 636-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7677439

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Cardiovascular autonomic dysfunction in primary Sjogren's syndrome. Author(s): Kovacs L, Paprika D, Takacs R, Kardos A, Varkonyi TT, Lengyel C, Kovacs A, Rudas L, Pokorny G. Source: Rheumatology (Oxford, England). 2004 January; 43(1): 95-9. Epub 2003 August 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12949253

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Caring for women living with Sjogren's syndrome. Author(s): Schoofs N. Source: Journal of Obstetric, Gynecologic, and Neonatal Nursing : Jognn / Naacog. 2003 September-October; 32(5): 589-93. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14565737

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CC chemokine receptor 5 and interleukin-1 receptor antagonist gene polymorphisms in patients with primary Sjogren's syndrome. Author(s): Petrek M, Cermakova Z, Hutyrova B, Micekova D, Drabek J, Rovensky J, Bosak V. Source: Clin Exp Rheumatol. 2002 September-October; 20(5): 701-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12412204

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CD40, CD154, Bax and Bcl-2 expression in Sjogren's syndrome salivary glands: a putative anti-apoptotic role during its effector phases. Author(s): Ohlsson M, Szodoray P, Loro LL, Johannessen AC, Jonsson R. Source: Scandinavian Journal of Immunology. 2002 December; 56(6): 561-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12472667

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Cells collected from the corneal surface in Sjogren's syndrome, dry eye, and normals. Author(s): Al-Oliky S, Begley C, Lowther G, Wilson G. Source: Advances in Experimental Medicine and Biology. 2002; 506(Pt B): 925-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12614011

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Cellular basis of ectopic germinal center formation and autoantibody production in the target organ of patients with Sjogren's syndrome. Author(s): Salomonsson S, Jonsson MV, Skarstein K, Brokstad KA, Hjelmstrom P, Wahren-Herlenius M, Jonsson R. Source: Arthritis and Rheumatism. 2003 November; 48(11): 3187-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14613282

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Central nervous system mechanisms in Sjogren's syndrome. Author(s): van Bijsterveld OP, Kruize AA, Bleys RL. Source: The British Journal of Ophthalmology. 2003 February; 87(2): 128-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12543734

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Classification criteria for Sjogren's syndrome. Author(s): Vitali C. Source: Annals of the Rheumatic Diseases. 2003 January; 62(1): 94-5; Author Reply 95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12480687

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Clinical and immunological characteristics of elderly onset Sjogren's syndrome: a comparison with younger onset disease. Author(s): Tishler M, Yaron I, Shirazi I, Yaron M. Source: The Journal of Rheumatology. 2001 April; 28(4): 795-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11327252

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Clinical and immunological factors associated with low lacrimal and salivary flow rate in patients with primary Sjogren's syndrome. Author(s): Pijpe J, Kalk WW, Vissink A. Source: The Journal of Rheumatology. 2003 January; 30(1): 206-7; Author Reply 207. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12508418

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Cogan's syndrome presenting as Sjogren's syndrome followed by acute aortic regurgitation. Author(s): Edrees A, Tran J, Thompson G, Watson KR, Godfrey W, Abdou NI. Source: Clinical Rheumatology. 2003 May; 22(2): 156. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12740685

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Comparison of immunoglobulin heavy chain rearrangements between peripheral and glandular B cells in a patient with primary Sjogren's syndrome. Author(s): Hansen A, Jacobi A, Pruss A, Kaufmann O, Scholze J, Lipsky PE, Dorner T. Source: Scandinavian Journal of Immunology. 2003 May; 57(5): 470-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12753504

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Comparison of lacrimal and salivary gland involvement in Sjogren's syndrome. Author(s): Vissink A, Kalk WW, Mansour K, Spijkervet FK, Bootsma H, Roodenburg JL, Kallenberg CG, Nieuw Amerongen AV. Source: Archives of Otolaryngology--Head & Neck Surgery. 2003 September; 129(9): 966-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12975269

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Comprehensive study of autonomic function in a population with primary Sjogren's syndrome. No evidence of autonomic involvement. Author(s): Niemela RK, Hakala M, Huikuri HV, Airaksinen KE. Source: The Journal of Rheumatology. 2003 January; 30(1): 74-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12508393

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Corneal blindness from end-stage Sjogren's syndrome and graft-versus-host disease. Author(s): Dohlman CH, Dudenhoefer EJ, Khan BF, Dohlman JG. Source: Advances in Experimental Medicine and Biology. 2002; 506(Pt B): 1335-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12614075

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Corneal innervation and morphology in primary Sjogren's syndrome. Author(s): Tuominen IS, Konttinen YT, Vesaluoma MH, Moilanen JA, Helinto M, Tervo TM. Source: Investigative Ophthalmology & Visual Science. 2003 June; 44(6): 2545-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12766055

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Correlation between interleukin 10 gene promoter region polymorphisms and clinical manifestations in Japanese patients with Sjogren's syndrome. Author(s): Origuchi T, Kawasaki E, Ide A, Kamachi M, Tanaka F, Ida H, Kawakami A, Migita K, Eguchi K. Source: Annals of the Rheumatic Diseases. 2003 November; 62(11): 1117-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14583579

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Correlations between nutrient intake and the polar lipid profiles of meibomian gland secretions in women with Sjogren's syndrome. Author(s): Sullivan BD, Cermak JM, Sullivan RM, Papas AS, Evans JE, Dana MR, Sullivan DA. Source: Advances in Experimental Medicine and Biology. 2002; 506(Pt A): 441-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12613944

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Critical hypokalemic renal tubular acidosis due to Sjogren's syndrome: association with the purported immune stimulant echinacea. Author(s): Logan JL, Ahmed J. Source: Clinical Rheumatology. 2003 May; 22(2): 158-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12740687

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Cystic lung disease in Sjogren's syndrome. Author(s): Hubscher O, Re R, Iotti R. Source: The Journal of Rheumatology. 2002 October; 29(10): 2235-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12375340

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D6S439 microsatellite identifies a new susceptibility region for primary Sjogren's syndrome. Author(s): Anaya JM, Rivera D, Palacio LG, Arcos-Burgos M, Correa PA. Source: The Journal of Rheumatology. 2003 October; 30(10): 2152-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14528509

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Defective cellular trafficking of lacrimal gland aquaporin-5 in Sjogren's syndrome. Author(s): Tsubota K, Hirai S, King LS, Agre P, Ishida N. Source: Lancet. 2001 March 3; 357(9257): 688-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11247557

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Dental and periodontal status of Sjogren's syndrome. Author(s): Boutsi EA, Paikos S, Dafni UG, Moutsopoulos HM, Skopouli FN. Source: Journal of Clinical Periodontology. 2000 April; 27(4): 231-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10783835

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Detecting abnormal regional cerebral blood flow in patients with primary Sjogren's syndrome by technetium-99m ethyl cysteinate dimer single photon emission computed tomography of the brain--a preliminary report. Author(s): Huang WS, Chiu PY, Kao A, Tsai CH, Lee CC. Source: Rheumatology International. 2003 July; 23(4): 174-7. Epub 2003 February 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12856142

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Detection of anti-SS-A/Ro and anti-SS-B/La antibodies of IgA and IgG isotypes in saliva and sera of patients with Sjogren's syndrome. Author(s): Iwasaki K, Okawa-Takatsuji M, Aotsuka S, Ono T. Source: Nihon Rinsho Meneki Gakkai Kaishi. 2003 December; 26(6): 346-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14752936

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Detection of HHV-8 sequences and antigens in a MALT lymphoma associated with Sjogren's syndrome. Author(s): Klussmann JP, Wagner M, Guntinas-Lichius O, Muller A. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2003 April; 32(4): 243-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12653865

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Detection of maternal-fetal microchimerism in the inflammatory lesions of patients with Sjogren's syndrome. Author(s): Kuroki M, Okayama A, Nakamura S, Sasaki T, Murai K, Shiba R, Shinohara M, Tsubouchi H. Source: Annals of the Rheumatic Diseases. 2002 December; 61(12): 1041-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12429532

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Detection of the tax gene of HTLV-I in labial salivary glands from patients with Sjogren's syndrome and other diseases of the oral cavity. Author(s): Mariette X, Agbalika F, Zucker-Franklin D, Clerc D, Janin A, Cherot P, Brouet JC. Source: Clin Exp Rheumatol. 2000 May-June; 18(3): 341-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10895371

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Development of autoimmune exocrinopathy resembling Sjogren's syndrome in estrogen-deficient mice of healthy background. Author(s): Ishimaru N, Arakaki R, Watanabe M, Kobayashi M, Miyazaki K, Hayashi Y. Source: American Journal of Pathology. 2003 October; 163(4): 1481-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14507655

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Diagnosis and definition of primary Sjogren's syndrome. Author(s): Gran JT. Source: Scandinavian Journal of Rheumatology. 2002; 31(2): 57-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12109647

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Diagnostic criteria and immunopathogenesis of Sjogren's syndrome: implications for therapy. Author(s): Kruize AA, Smeenk RJ, Kater L. Source: Immunology Today. 1995 December; 16(12): 557-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8579745

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Different airway responsiveness profiles in atopic asthma, nonatopic asthma, and Sjogren's syndrome. BHR Study Group. Bronchial hyperresponsiveness. Author(s): Ludviksdottir D, Janson C, Bjornsson E, Stalenheim G, Boman G, Hedenstrom H, Venge P, Gudbjornsson B, Valtysdottir S. Source: Allergy. 2000 March; 55(3): 259-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10753017

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Differential expression of matrix metalloproteinases in labial salivary glands of patients with primary Sjogren's syndrome. Author(s): Perez P, Goicovich E, Alliende C, Aguilera S, Leyton C, Molina C, Pinto R, Romo R, Martinez B, Gonzalez MJ. Source: Arthritis and Rheumatism. 2000 December; 43(12): 2807-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11145040

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Diminished peripheral blood memory B cells and accumulation of memory B cells in the salivary glands of patients with Sjogren's syndrome. Author(s): Hansen A, Odendahl M, Reiter K, Jacobi AM, Feist E, Scholze J, Burmester GR, Lipsky PE, Dorner T. Source: Arthritis and Rheumatism. 2002 August; 46(8): 2160-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12209521

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Disproportion of helper T cell subsets in peripheral blood of patients with primary Sjogren's syndrome. Author(s): Kohriyama K, Katayama Y. Source: Autoimmunity. 2000; 32(1): 67-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10958177

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Distribution of salivary aquaporin-5 in Sjogren's syndrome. Author(s): Groneberg DA, Peiser C, Fischer A. Source: Lancet. 2002 May 18; 359(9319): 1778-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12049894

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Distribution of salivary aquaporin-5 in Sjogren's syndrome. Author(s): Steinfeld SD, Delporte C. Source: Lancet. 2002 May 18; 359(9319): 1777-8; Author Reply 1778. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12049892

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Do autoantibodies predict autoimmune liver disease in primary Sjogren's syndrome? Data of 180 patients upon a 5 year follow-up. Author(s): Csepregi A, Szodoray P, Zeher M. Source: Scandinavian Journal of Immunology. 2002 December; 56(6): 623-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12472675

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Do estrogen and progesterone play a role in the dry eye of Sjogren's syndrome? Author(s): Suzuki T, Schaumberg DA, Sullivan BD, Liu M, Richards SM, Sullivan RM, Dana MR, Sullivan DA. Source: Annals of the New York Academy of Sciences. 2002 June; 966: 223-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12114275

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Does pantoprazole alleviate mouth dryness in patients with Sjogren's syndrome? Author(s): Fiebiger W, Stummvoll G, Weinlander G, Raderer M. Source: Rheumatology (Oxford, England). 2001 January; 40(1): 110. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11157153

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Economic and quality of life impact of dry eye symptoms in women with Sjogren's syndrome. Author(s): Sullivan RM, Cermak JM, Papas AS, Dana MR, Sullivan DA. Source: Advances in Experimental Medicine and Biology. 2002; 506(Pt B): 1183-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12614049

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Ectopic expression of the B cell-attracting chemokine BCA-1 (CXCL13) on endothelial cells and within lymphoid follicles contributes to the establishment of germinal center-like structures in Sjogren's syndrome. Author(s): Amft N, Curnow SJ, Scheel-Toellner D, Devadas A, Oates J, Crocker J, Hamburger J, Ainsworth J, Mathews J, Salmon M, Bowman SJ, Buckley CD. Source: Arthritis and Rheumatism. 2001 November; 44(11): 2633-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11710719

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Effect of xerostomic medications on stimulated salivary flow rate in patients with Sjogren's syndrome. Author(s): Simmons DD, Al-Hashimi I, Haghighat N. Source: Quintessence Int. 2000 March; 31(3): 196-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11203926

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Effects of mouthrinses with linseed extract Salinum without/with chlorhexidine on oral conditions in patients with Sjogren's syndrome. A double-blind crossover investigation. Author(s): Johansson G, Andersson G, Edwardsson S, Bjorn AL, Manthorpe R, Attstrom R. Source: Gerodontology. 2001 December; 18(2): 87-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11794743

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Elevated blood pressure is not related to saliva flow in patients with Sjogren's syndrome. Author(s): Sankar V, Brennan MT, Radfar L, Leakan RA, Pillemer SR. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2002 August; 94(2): 179-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12221385

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Elevated interleukin-6 plasma levels are regulated by the promoter region polymorphism of the IL6 gene in primary Sjogren's syndrome and correlate with the clinical manifestations of the disease. Author(s): Hulkkonen J, Pertovaara M, Antonen J, Pasternack A, Hurme M. Source: Rheumatology (Oxford, England). 2001 June; 40(6): 656-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11426023

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Enhanced degradation of proteins of the basal lamina and stroma by matrix metalloproteinases from the salivary glands of Sjogren's syndrome patients: correlation with reduced structural integrity of acini and ducts. Author(s): Goicovich E, Molina C, Perez P, Aguilera S, Fernandez J, Olea N, Alliende C, Leyton C, Romo R, Leyton L, Gonzalez MJ. Source: Arthritis and Rheumatism. 2003 September; 48(9): 2573-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13130477

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Enhanced DNA damage-induced p53 peptide phosphorylation and cell-cycle arrest in Sjogren's syndrome cells. Author(s): Henriksson G, Brant M, Sallmyr A, Fukushima S, Manthorpe R, Bredberg A. Source: European Journal of Clinical Investigation. 2002 June; 32(6): 458-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12059992

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Epidemiology of Sjogren's syndrome, especially its primary form. Author(s): Manthorpe R, Jacobsson LT, Kirtava Z, Theander E. Source: Annales De Medecine Interne. 1998 February; 149(1): 7-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11490520

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Epstein-Barr virus (types 1 and 2) in the tear film in Sjogren's syndrome and HIV infection. Author(s): Willoughby CE, Baker K, Kaye SB, Carey P, O'Donnell N, Field A, Longman L, Bucknall R, Hart CA. Source: Journal of Medical Virology. 2002 November; 68(3): 378-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12226825

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Epstein-Barr virus, methotrexate, and lymphoma in patients with rheumatoid arthritis and primary Sjogren's syndrome: case series. Author(s): Dawson TM, Starkebaum G, Wood BL, Willkens RF, Gown AM. Source: The Journal of Rheumatology. 2001 January; 28(1): 47-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11196542

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Erythematous swelling of the lip associated with Sjogren's syndrome and mimicking cheilitis granulomatosa. Author(s): Fujimura T, Aiba S, Suetake T, Tagami H. Source: The Journal of Dermatology. 2001 January; 28(1): 47-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11280465

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Estimation of Sjogren's syndrome among IBD patients. A six year post-diagnostic prevalence study. Author(s): Palm O, Moum B, Gran JT. Source: Scandinavian Journal of Rheumatology. 2002; 31(3): 140-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12195627

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Etanercept in the treatment of patients with primary Sjogren's syndrome: a pilot study. Author(s): Zandbelt MM, de Wilde P, van Damme P, Hoyng CB, van de Putte L, van den Hoogen F. Source: The Journal of Rheumatology. 2004 January; 31(1): 96-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14705226

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Exposure to silica and primary Sjogren's syndrome in a dental technician. Author(s): Astudillo L, Sailler L, Ecoiffier M, Giron J, Couret B, Arlet-Suau E. Source: Rheumatology (Oxford, England). 2003 October; 42(10): 1268-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14508049

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Expression of cyclooxygenase-1 (COX-1) in labial salivary glands of Sjogren's syndrome. Author(s): Tominaga M, Migita K, Sano H, Fukui W, Kohno M, Tsubouchi Y, Honda S, Fukuda T, Nakamura H, Yamasaki S, Kawabe Y, Kawakami A, Eguchi K. Source: Clinical and Experimental Immunology. 2000 December; 122(3): 459-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11122255

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Expression of the B cell-attracting chemokine CXCL13 in the target organ and autoantibody production in ectopic lymphoid tissue in the chronic inflammatory disease Sjogren's syndrome. Author(s): Salomonsson S, Larsson P, Tengner P, Mellquist E, Hjelmstrom P, WahrenHerlenius M. Source: Scandinavian Journal of Immunology. 2002 April; 55(4): 336-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11967114

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Expression of the interferon-gamma-inducible 10-kd protein and CXC receptor 3 in the salivary gland lesions of patients with Sjogren's syndrome: comment on the article by Ogawa et al. Author(s): Sfriso P, Calabrese F, Grava C, Agostini C, Punzi L, Oliviero F, Botsios C, Ostuni PA, Todesco S. Source: Arthritis and Rheumatism. 2003 August; 48(8): 2390-1; Author Reply 2391-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12905497

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Expression of TNF-related apoptosis inducing ligand (TRAIL) on infiltrating cells and of TRAIL receptors on salivary glands in patients with Sjogren's syndrome. Author(s): Matsumura R, Umemiya K, Kagami M, Tomioka H, Tanabe E, Sugiyama T, Sueishi M, Kayagaki N, Yagita H, Okumura K. Source: Clin Exp Rheumatol. 2002 November-December; 20(6): 791-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12508770

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Extrasalivary lymphoma development in Sjogren's syndrome: clonal evolution from parotid gland lymphoproliferation and role of local triggering. Author(s): Gasparotto D, De Vita S, De Re V, Marzotto A, De Marchi G, Scott CA, Gloghini A, Ferraccioli G, Boiocchi M. Source: Arthritis and Rheumatism. 2003 November; 48(11): 3181-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14613281

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F-18 FDG positron emission tomography demonstrates resolution of non-Hodgkin's lymphoma of the parotid gland in a patient with Sjogren's syndrome: before and after anti-CD20 antibody rituximab therapy. Author(s): Shih WJ, Ghesani N, Hongming Z, Alavi A, Schusper S, Mozley D. Source: Clinical Nuclear Medicine. 2002 February; 27(2): 142-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11786752

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Factors predictive of renal involvement in patients with primary Sjogren's syndrome. Author(s): Pertovaara M, Korpela M, Pasternack A. Source: Clinical Nephrology. 2001 July; 56(1): 10-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11499654

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Failure of G-CSF therapy in neutropenia associated with Sjogren's syndrome. Author(s): Vivancos J, Vila M, Serra A, Loscos J, Anguita A. Source: Rheumatology (Oxford, England). 2002 April; 41(4): 471-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11961184

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Failure to detect antibodies to extracellular loop peptides of the muscarinic M3 receptor in primary Sjogren's syndrome. Author(s): Cavill D, Waterman SA, Gordon TP. Source: The Journal of Rheumatology. 2002 June; 29(6): 1342-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12064859

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Failure to detect antibodies to the second extracellular loop of the serotonin 5-HT4 receptor in systemic lupus erythematosus and primary Sjogren's syndrome. Author(s): Cavill D, Waterman S, Gordon TP. Source: Lupus. 2002; 11(3): 197-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11999887

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Failure to detect human papillomavirus in primary Sjogren's syndrome. Author(s): Steinfeld S, Noel JC, Appelboom T. Source: Arthritis and Rheumatism. 1999 May; 42(5): 1064-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10323467

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Fas and Fas ligand gene polymorphisms in primary Sjogren's syndrome. Author(s): Bolstad AI, Wargelius A, Nakken B, Haga HJ, Jonsson R. Source: The Journal of Rheumatology. 2000 October; 27(10): 2397-405. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11036836

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Fas and Fas-mediated effects on a human salivary cell line in vitro: a model for immune-mediated exocrine damage in Sjogren's syndrome. Author(s): Gannot G, Bermudez D, Lillibridge D, Fox PC. Source: Cell Death and Differentiation. 1998 September; 5(9): 743-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10200533

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Fas gene promoter polymorphisms in primary Sjogren's syndrome. Author(s): Mullighan CG, Heatley S, Lester S, Rischmueller M, Gordon TP, Bardy PG. Source: Annals of the Rheumatic Diseases. 2004 January; 63(1): 98-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14672901

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Fas-induced apoptosis is a rare event in Sjogren's syndrome. Author(s): Ohlsson M, Skarstein K, Bolstad AI, Johannessen AC, Jonsson R. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2001 January; 81(1): 95-105. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11204278

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Fatal scleroderma renal crisis caused by gastrointestinal bleeding in a patient with scleroderma, Sjogren's syndrome and primary biliary cirrhosis overlap. Author(s): Szigeti N, Fabian G, Czirjak L. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2002 May; 16(3): 276-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12195572

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Fatigue and immune activity in Sjogren's syndrome. Author(s): Bax HI, Vriesendorp TM, Kallenberg CG, Kalk WW. Source: Annals of the Rheumatic Diseases. 2002 March; 61(3): 284. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11830450

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Fatigue in daily life in patients with primary Sjogren's syndrome and systemic lupus erythematosus. Author(s): Godaert GL, Hartkamp A, Geenen R, Garssen A, Kruize AA, Bijlsma JW, Derksen RH. Source: Annals of the New York Academy of Sciences. 2002 June; 966: 320-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12114289

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Fatigue in primary Sjogren's syndrome: is there a link with the fibromyalgia syndrome? Author(s): Giles I, Isenberg D. Source: Annals of the Rheumatic Diseases. 2000 November; 59(11): 875-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11053064

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Fetal microchimerism in Sjogren's syndrome. Author(s): Mijares-Boeckh-Behrens T, Selva-O'Callaghan A, Solans-Laque R, Bosch-Gil JA, Vilardell-Tarres M, Balada-Prades E. Source: Annals of the Rheumatic Diseases. 2001 September; 60(9): 897-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11534505

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Fibromyalgia in Italian patients with primary Sjogren's syndrome. Author(s): Ostuni P, Botsios C, Sfriso P, Punzi L, Chieco-Bianchi F, Semerano L, Grava C, Todesco S. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2002 January; 69(1): 51-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11858357

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Five-year efficacy of intravenous gammaglobulin to treat dysautonomia in Sjogren's syndrome. Author(s): Dupond JL, Gil H, de Wazieres B. Source: The American Journal of Medicine. 1999 January; 106(1): 125. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10320132

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Frequency and evaluation of t(14;18) translocation in Sjogren's syndrome. Author(s): Takacs I, Zeher M, Urban L, Bachmann M, Szegedi G, Semsei I. Source: Annals of Hematology. 2000 August; 79(8): 444-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10985364

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Frequency and predictive value of the clinical manifestations in Sjogren's syndrome. Author(s): Al-Hashimi I, Khuder S, Haghighat N, Zipp M. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2001 January; 30(1): 1-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11140894

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Fungal load and candidiasis in Sjogren's syndrome. Author(s): Radfar L, Shea Y, Fischer SH, Sankar V, Leakan RA, Baum BJ, Pillemer SR. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2003 September; 96(3): 283-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12973284

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Gammalinolenic acid treatment of fatigue associated with primary Sjogren's syndrome. Author(s): Theander E, Horrobin DF, Jacobsson LT, Manthorpe R. Source: Scandinavian Journal of Rheumatology. 2002; 31(2): 72-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12109650

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Gastric antral vascular ectasia (watermelon stomach) in a patient with Sjogren's syndrome. Author(s): Goel A, Christian CL. Source: The Journal of Rheumatology. 2003 May; 30(5): 1090-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12734912

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Gastric involvement in primary Sjogren's syndrome. Author(s): Ostuni PA, Germana B, Di Mario F, Rugge M, Plebani M, De Zambiasi P, Naccarato R, Gambari PF. Source: Clin Exp Rheumatol. 1993 January-February; 11(1): 21-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8453793

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Gastritis classified in accordance with the Sydney system in patients with primary Sjogren's syndrome. Author(s): Collin P, Karvonen AL, Korpela M, Laippala P, Helin H. Source: Scandinavian Journal of Gastroenterology. 1997 February; 32(2): 108-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9051869

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Gastrointestinal manifestations of Sjogren's syndrome. Author(s): Triantafillidis JK. Source: The American Journal of Gastroenterology. 1995 September; 90(9): 1541. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7661194

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Genetic aspects of Sjogren's syndrome. Author(s): Bolstad AI, Jonsson R. Source: Arthritis Research. 2002; 4(6): 353-9. Epub 2002 September 24. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12453311

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Genetic association between interleukin-10 promoter region polymorphisms and primary Sjogren's syndrome. Author(s): Hulkkonen J, Pertovaara M, Antonen J, Lahdenpohja N, Pasternack A, Hurme M. Source: Arthritis and Rheumatism. 2001 January; 44(1): 176-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11212157

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Genomic absence of the gene encoding T cell receptor Vbeta7.2 is linked to the presence of autoantibodies in Sjogren's syndrome. Author(s): Manavalan SJ, Valiando JR, Reeves WH, Arnett FC, Necker A, Simantov R, Lyons R, Satoh M, Posnett DN. Source: Arthritis and Rheumatism. 2004 January; 50(1): 187-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14730616

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Gingival and periodontal health in Sjogren's syndrome and other connective tissue diseases. Author(s): Mutlu S, Richards A, Maddison P, Porter S, Scully C. Source: Clin Exp Rheumatol. 1993 January-February; 11(1): 95-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8453807

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Gingival impression: a new biological test for xerostomia in diagnosis of Sjogren's syndrome. Author(s): Liotet S, Wattiaux MJ, Morin Y. Source: Advances in Experimental Medicine and Biology. 1994; 350: 655-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8030551

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Glandular and extraglandular expression of costimulatory molecules in patients with Sjogren's syndrome. Author(s): Matsumura R, Umemiya K, Goto T, Nakazawa T, Kagami M, Tomioka H, Tanabe E, Sugiyama T, Sueishi M. Source: Annals of the Rheumatic Diseases. 2001 May; 60(5): 473-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11302869

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Glandular and extraglandular expression of the Fas-Fas ligand and apoptosis in patients with Sjogren's syndrome. Author(s): Matsumura R, Umemiya K, Kagami M, Tomioka H, Tanabe E, Sugiyama T, Sueishi M, Nakajima A, Azuma M, Okumura K, Sumida T. Source: Clin Exp Rheumatol. 1998 September-October; 16(5): 561-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9779303

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Glomerular filtration rate in primary Sjogren's syndrome with renal disease. Author(s): Eriksson P, Denneberg T, Granerus G, Lindstrom F. Source: Scandinavian Journal of Urology and Nephrology. 1996 April; 30(2): 121-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8738057

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Granzyme A and perforin expressed in the lacrimal glands of patients with Sjogren's syndrome. Author(s): Tsubota K, Saito I, Miyasaka N. Source: American Journal of Ophthalmology. 1994 January 15; 117(1): 120-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7904795

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Guess what! Cutaneous sarcoidosis, Sjogren's syndrome and autoimmune thyroiditis associated with hepatitis C virus infection. Author(s): Belgodere X, Viraben R, Gorguet B, Allaouchiche B, Lieutaud O, Maestracci D. Source: European Journal of Dermatology : Ejd. 1999 April-May; 9(3): 235-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10408919

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Gynaecological aspects of primary Sjogren's syndrome. Author(s): Marchesoni D, Mozzanega B, De Sandre P, Romagnolo C, Gambari PF, Maggino T. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 1995 November; 63(1): 49-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8674565

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Gynecologic manifestations of Sjogren's syndrome. Author(s): Lehrer S, Bogursky E, Yemini M, Kase NG, Birkenfeld A. Source: American Journal of Obstetrics and Gynecology. 1994 March; 170(3): 835-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8141212

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Haematopoietic stem cell transplantation (HSCT) in a patient with Sjogren's syndrome and lung malt lymphoma cured lymphoma not the autoimmune disease. Author(s): Ferraccioli G, Damato R, De Vita S, Fanin R, Damiani D, Baccarani M. Source: Annals of the Rheumatic Diseases. 2001 February; 60(2): 174-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11203719

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Health-related quality of life in patients with primary Sjogren's syndrome and xerostomia: a comparative study. Author(s): Rostron J, Rogers S, Longman L, Kaney S, Field EA. Source: Gerodontology. 2002 July; 19(1): 53-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12164241

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Hearing loss evaluation of Sjogren's syndrome using distortion product otoacoustic emissions. Author(s): Hatzopoulos S, Amoroso C, Aimoni C, Lo Monaco A, Govoni M, Martini A. Source: Acta Otolaryngol Suppl. 2002; (548): 20-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12211351

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Hearing loss in Sjogren's syndrome patients. A comparative study. Author(s): Ziavra N, Politi EN, Kastanioudakis I, Skevas A, Drosos AA. Source: Clin Exp Rheumatol. 2000 November-December; 18(6): 725-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11138335

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Heart rate variability in patients with Sjogren's syndrome. Author(s): Tumiati B, Perazzoli F, Negro A, Pantaleoni M, Regolisti G. Source: Clinical Rheumatology. 2000; 19(6): 477-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11147760

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Hepatitis C virus infection in patients with Sjogren's syndrome and non-Hodgkin's lymphoma: comment on the article by Voulgarelis et al. Author(s): Drucker Y. Source: Arthritis and Rheumatism. 2000 May; 43(5): 1187. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10817577

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Hepatitis C virus: a common triggering factor for both nodular vasculitis and Sjogren's syndrome? Author(s): Cardinali C, Gerlini G, Caproni M, Pimpinelli N, Fabbri P. Source: The British Journal of Dermatology. 2000 January; 142(1): 187-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10819552

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High circulating levels of soluble scavenger receptors (sCD5 and sCD6) in patients with primary Sjogren's syndrome. Author(s): Ramos-Casals M, Font J, Garcia-Carrasco M, Calvo J, Places L, Padilla O, Cervera R, Bowen MA, Lozano F, Ingelmo M. Source: Rheumatology (Oxford, England). 2001 September; 40(9): 1056-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11561119

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High frequency of primary Sjogren's syndrome in Taiwanese patients presenting as relapsing-remitting multiple sclerosis. Author(s): Wang YJ, Tsai KY, Fuh JL, Tsai CP, Wang SJ. Source: European Neurology. 2004; 51(1): 21-5. Epub 2003 November 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14631125

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Histopathology of renal biopsies with correlation to clinical findings in primary Sjogren's syndrome. Author(s): Enestrom S, Denneberg T, Eriksson P. Source: Clin Exp Rheumatol. 1995 November-December; 13(6): 697-703. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8835241

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HLA markers and clinical characteristics in Caucasians with primary Sjogren's syndrome. Author(s): Bolstad AI, Wassmuth R, Haga HJ, Jonsson R. Source: The Journal of Rheumatology. 2001 July; 28(7): 1554-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11469461

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HLA system and autoantibodies in primary Sjogren's syndrome. Author(s): Panchovska M, Sheytanov Y, Martinova F. Source: Bratisl Lek Listy. 2002; 103(1): 41-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12061088

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HLA-DQB1 CAR1/CAR2, TNFa IR2/IR4 and CTLA-4 polymorphisms in Tunisian patients with rheumatoid arthritis and Sjogren's syndrome. Author(s): Hadj Kacem H, Kaddour N, Adyel FZ, Bahloul Z, Ayadi H. Source: Rheumatology (Oxford, England). 2001 December; 40(12): 1370-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11752507

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How should we interpret the lower lip biopsy finding in patients investigated for Sjogren's syndrome? Author(s): Manthorpe R. Source: Arthritis and Rheumatism. 2002 April 15; 47(2): 114-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11954002

Studies

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How significant is sensorineural hearing loss in primary Sjogren's syndrome? An individually matched case-control study. Author(s): Boki KA, Ioannidis JP, Segas JV, Maragkoudakis PV, Petrou D, Adamopoulos GK, Moutsopoulos HM. Source: The Journal of Rheumatology. 2001 April; 28(4): 798-801. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11327253

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HTLV-I associated uveitis, myelopathy, rheumatoid arthritis and Sjogren's syndrome. Author(s): Pinheiro SR, Lana-Peixoto MA, Proietti AB, Orefice F, Lima-Martins MV, Proietti FA. Source: Arquivos De Neuro-Psiquiatria. 1995 December; 53(4): 777-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8729772

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Human ABCA1 contains a large amino-terminal extracellular domain homologous to an epitope of Sjogren's Syndrome. Author(s): Tanaka AR, Ikeda Y, Abe-Dohmae S, Arakawa R, Sadanami K, Kidera A, Nakagawa S, Nagase T, Aoki R, Kioka N, Amachi T, Yokoyama S, Ueda K. Source: Biochemical and Biophysical Research Communications. 2001 May 25; 283(5): 1019-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11355874

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Humoral immunity to Ro52 is not associated with the Ro52 9571 C/T polymorphism in Australian patients with primary Sjogren's syndrome. Author(s): Lester S, Danda D, Cavill D, Pile K, Downie-Doyle S, Rischmueller M. Source: Arthritis and Rheumatism. 2003 November; 48(11): 3293-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14613296

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Hyporeninemic hypoaldosteronism associated with Sjogren's syndrome. Author(s): Onozaki A, Katoh T, Watanabe T. Source: The American Journal of Medicine. 2002 February 15; 112(3): 245-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11893359

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Hypothalamus-hypophysis-thyroid axis, triiodothyronine and antithyroid antibodies in patients with primary and secondary Sjogren's syndrome. Author(s): Ozgen AG, Keser G, Erdem N, Aksu K, Gumusdis G, Kabalak T, Doganavsargil E. Source: Clinical Rheumatology. 2001; 20(1): 44-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11254240

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Sjogren's Syndrome

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IGF-1 and insulin receptor expression in the minor salivary gland tissues of Sjogren's syndrome and mucoceles--immunohistochemical study. Author(s): Katz J, Stavropoulos F, Cohen D, Robledo J, Stewart C, Heft M. Source: Oral Diseases. 2003 January; 9(1): 7-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12617251

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IgG and IgM antiganglioside M1 antibodies in primary Sjogren's syndrome with and without peripheral neuropathy. Author(s): Giordano N, Lucani B, Amendola A, Geraci S, Santacroce C, Gennari C, Hartini G, Nuti R. Source: Clinical Rheumatology. 2003 September; 22(3): 256-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14505225

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IL-1 gene family haplotypes and Raynaud's phenomenon in primary Sjogren's syndrome. Author(s): Hulkkonen J, Pertovaara M, Antonen J, Pasternack A, Hurme M. Source: Rheumatology (Oxford, England). 2002 October; 41(10): 1206-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12364651

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Immunglobulin repertoire analysis provides new insights into the immunopathogenesis of Sjogren's syndrome. Author(s): Dorner T, Hansen A, Jacobi A, Lipsky PE. Source: Autoimmunity Reviews. 2002 May; 1(3): 119-24. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12849004

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Immunopathogenesis of Sjogren's syndrome. Author(s): Borchers AT, Naguwa SM, Keen CL, Gershwin ME. Source: Clinical Reviews in Allergy & Immunology. 2003 August; 25(1): 89-104. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12794264

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Improvement in Sjogren's syndrome following therapy with rituximab for marginal zone lymphoma. Author(s): Somer BG, Tsai DE, Downs L, Weinstein B, Schuster SJ; American College of Rheumatology ad hoc Committee on Immunologic Testing Guidelines. Source: Arthritis and Rheumatism. 2003 June 15; 49(3): 394-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12794796

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In primary Sjogren's syndrome, HLA class II is associated exclusively with autoantibody production and spreading of the autoimmune response. Author(s): Gottenberg JE, Busson M, Loiseau P, Cohen-Solal J, Lepage V, Charron D, Sibilia J, Mariette X. Source: Arthritis and Rheumatism. 2003 August; 48(8): 2240-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12905478

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Incidence of Sjogren's syndrome in Japanese patients with hepatitis C virus infection. Author(s): Nagao Y, Hanada S, Shishido S, Ide T, Kumashiro R, Ueno T, Sata M. Source: Journal of Gastroenterology and Hepatology. 2003 March; 18(3): 258-66. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12603525

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Increased salivary gland tissue expression of Fas, Fas ligand, cytotoxic T lymphocyteassociated antigen 4, and programmed cell death 1 in primary Sjogren's syndrome. Author(s): Bolstad AI, Eiken HG, Rosenlund B, Alarcon-Riquelme ME, Jonsson R. Source: Arthritis and Rheumatism. 2003 January; 48(1): 174-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12528117

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Increased severity of lower urinary tract symptoms and daytime somnolence in primary Sjogren's syndrome. Author(s): Walker J, Gordon T, Lester S, Downie-Doyle S, McEvoy D, Pile K, Waterman S, Rischmueller M. Source: The Journal of Rheumatology. 2003 November; 30(11): 2406-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14677185

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Increased soluble CD23 molecules in serum/saliva and correlation with the stage of sialoectasis in patients with primary Sjogren's syndrome. Author(s): Takei M, Azuhata T, Yoshimatu T, Shigihara S, Hashimoto S, Horie T, Horikoshi A, Sawada S. Source: Clin Exp Rheumatol. 1995 November-December; 13(6): 711-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8835243

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Infliximab in primary Sjogren's syndrome: one-year followup. Author(s): Steinfeld SD, Demols P, Appelboom T. Source: Arthritis and Rheumatism. 2002 December; 46(12): 3301-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12483735

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Infliximab therapy in patients with secondary Sjogren's syndrome: functional evaluation. Author(s): Martin Martin LS, Migliore A, Todino V, Pagano A, Chianelli M. Source: Clin Exp Rheumatol. 2003 May-June; 21(3): 412. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12846076

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Interleukin 10 (IL-10) influences autoimmune response in primary Sjogren's syndrome and is linked to IL-10 gene polymorphism. Author(s): Anaya JM, Correa PA, Herrera M, Eskdale J, Gallagher G. Source: The Journal of Rheumatology. 2002 September; 29(9): 1874-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12233881

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Sjogren's Syndrome

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Interleukin 1beta and tumour necrosis factor alpha secreting cells are increased in the peripheral blood of patients with primary Sjogren's syndrome. Author(s): Willeke P, Schotte H, Schluter B, Erren M, Becker H, Dyong A, Mickholz E, Domschke W, Gaubitz M. Source: Annals of the Rheumatic Diseases. 2003 April; 62(4): 359-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12634239

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Interstitial cystitis-like urinary symptoms among patients with Sjogren's syndrome: a population-based study in Finland. Author(s): Leppilahti M, Tammela TL, Huhtala H, Kiilholma P, Leppilahti K, Auvinen A. Source: The American Journal of Medicine. 2003 July; 115(1): 62-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12867237

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Interstitial nephritis with infiltration of IgG-kappa positive plasma cells in a patient with Sjogren's syndrome. Author(s): Pijpe J, Vissink A, Van der Wal JE, Kallenberg CG. Source: Rheumatology (Oxford, England). 2004 January; 43(1): 108-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14681564

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Involvement of the interferon-gamma-induced T cell-attracting chemokines, interferon-gamma-inducible 10-kd protein (CXCL10) and monokine induced by interferon-gamma (CXCL9), in the salivary gland lesions of patients with Sjogren's syndrome. Author(s): Ogawa N, Ping L, Zhenjun L, Takada Y, Sugai S. Source: Arthritis and Rheumatism. 2002 October; 46(10): 2730-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12384933

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Involvement of the nervous system and HLA phenotype in primary Sjogren's syndrome. Author(s): Panchovska MS, Sheitanov YI, Martinova FG. Source: Minerva Med. 2003 February; 94(1): 57-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12719703

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Isolated necrotizing and granulomatous vasculitis causing ischemic bowel disease in primary Sjogren's syndrome. Author(s): Lie JT. Source: The Journal of Rheumatology. 1995 December; 22(12): 2375-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8965277

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Jaccoud's arthropathy in primary Sjogren's syndrome with benign hypergammaglobulinaemic purpura. Author(s): M'Rad S, Ben Miled K, Makni S, Kchir M, Ennafaa M, Harmel A, Hendaoui L, Mzabi S, el Haddad ML, Ben Dridi M. Source: Eur J Med. 1993 June-July; 2(6): 373-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8252186

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Juvenile dermatomyositis and Sjogren's syndrome occurring concurrently in an adolescent male. Author(s): Cody D, Davidson J. Source: Rheumatology (Oxford, England). 2002 June; 41(6): 698-700. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12048300

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Juvenile onset of primary Sjogren's syndrome: report of 10 cases. Author(s): Ostuni PA, Ianniello A, Sfriso P, Mazzola G, Andretta M, Gambari PF. Source: Clin Exp Rheumatol. 1996 November-December; 14(6): 689-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8978969

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Keratoconjunctitis sicca versus dry mouth and autoantibodies in primary and secondary Sjogren's syndrome. Author(s): Kitagawa K, Nakamura T, Sugai S. Source: Advances in Experimental Medicine and Biology. 2002; 506(Pt B): 1195-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12614051

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Keratoconjunctivitis sicca and primary Sjogren's syndrome in a Danish population aged 30-60 years. Author(s): Bjerrum KB. Source: Acta Ophthalmologica Scandinavica. 1997 June; 75(3): 281-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9253975

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Kidney injury in Sjogren's syndrome. Author(s): Skopouli FN. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2001; 16 Suppl 6: 634. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11568246

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Kininogen-kallikrein-kinin system in plasma and saliva of patients with Sjogren's syndrome. Author(s): Hernandez CC, Donadi EA, Reis ML. Source: The Journal of Rheumatology. 1998 December; 25(12): 2381-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9858433

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Sjogren's Syndrome

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Knee joint synovitis in Sjogren's syndrome. Sonographic study. Author(s): Iagnocco A, Coari G, Palombi G, Valesini G. Source: Scandinavian Journal of Rheumatology. 2002; 31(5): 291-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12455820

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Ku protein and DNA strand breaks in lip glands of normal and primary Sjogren's syndrome subjects: lack of correlation with apoptosis. Author(s): Larsson A, Henriksson G, Manthorpe R, Sallmyr A, Bredberg A. Source: Scandinavian Journal of Immunology. 2001 September; 54(3): 328-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11555398

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Lack of evidence for an increased microchimerism in the circulation of patients with Sjogren's syndrome. Author(s): Toda I, Kuwana M, Tsubota K, Kawakami Y. Source: Annals of the Rheumatic Diseases. 2001 March; 60(3): 248-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11171687

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Local production of Ro/SSA and La/SSB autoantibodies in the target organ coincides with high levels of circulating antibodies in sera of patients with Sjogren's syndrome. Author(s): Salomonsson S, Wahren-Herlenius M. Source: Scandinavian Journal of Rheumatology. 2003; 32(2): 79-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12737325

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Locus DR in primary Sjogren's syndrome. Author(s): Panchovska M, Sheitanov Y, Martinova F. Source: Bratisl Lek Listy. 2001; 102(8): 382. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11763672

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Longlasting effects of immunoadsorption in severe Sjogren's syndrome. Author(s): Bohm M, Dorner T, Knebel F, Bruns A, Jochmann N, Baumann G. Source: Annals of the Rheumatic Diseases. 2004 February; 63(2): 214-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14722217

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Long-term risk of mortality and lymphoproliferative disease and predictive classification of primary Sjogren's syndrome. Author(s): Ioannidis JP, Vassiliou VA, Moutsopoulos HM. Source: Arthritis and Rheumatism. 2002 March; 46(3): 741-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11920410

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Low grade marginal zone B cell lymphoma of the breast associated with localised amyloidosis and corpora amylacea in a woman with long standing primary Sjogren's syndrome. Author(s): Kambouchner M, Godmer P, Guillevin L, Raphael M, Droz D, Martin A. Source: Journal of Clinical Pathology. 2003 January; 56(1): 74-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12499440

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Low serum dehydroepiandrosterone sulfate in women with primary Sjogren's syndrome as an isolated sign of impaired HPA axis function. Author(s): Valtysdottir ST, Wide L, Hallgren R. Source: The Journal of Rheumatology. 2001 June; 28(6): 1259-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11409117

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Lymphocytic interstitial pneumonitis associated with Epstein-Barr virus in Systemic Lupus Erythematosus and Sjogren's Syndrome. Complete remission with corticosteriod and cyclophosphamide. Author(s): Yum HK, Kim ES, Ok KS, Lee HK, Choi SJ. Source: Korean J Intern Med. 2002 September; 17(3): 198-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12298431

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Lymphomas complicating Sjogren's syndrome and hepatitis C virus infection may share a common pathogenesis: chronic stimulation of rheumatoid factor B cells. Author(s): Mariette X. Source: Annals of the Rheumatic Diseases. 2001 November; 60(11): 1007-10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11602464

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Lymphomatoid papulosis associated with Sjogren's syndrome. Author(s): Yamamoto T, Ohi M, Nishioka K. Source: The Journal of Dermatology. 2002 March; 29(3): 174-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11990256

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Lymphoproliferation in autoimmunity and Sjogren's syndrome. Author(s): Voulgarelis M, Moutsopoulos HM. Source: Curr Rheumatol Rep. 2003 August; 5(4): 317-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14531960

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Manometric assessment of impaired esophageal motor function in primary Sjogren's syndrome. Author(s): Rosztoczy A, Kovacs L, Wittmann T, Lonovics J, Pokorny G. Source: Clin Exp Rheumatol. 2001 March-April; 19(2): 147-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11326475

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Massive splenomegaly and hypersplenism in a young woman with primary Sjogren's syndrome. Author(s): Appel H, Loddenkemper C, Rohweder J, Rudwaleit M, Zeitz M, Sieper J. Source: The Journal of Rheumatology. 2002 September; 29(9): 2012-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12233900

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Mental wellbeing and quality of sexual life in women with primary Sjogren's syndrome are related to circulating dehydroepiandrosterone sulphate. Author(s): Valtysdottir ST, Wide L, Hallgren R. Source: Annals of the Rheumatic Diseases. 2003 September; 62(9): 875-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12922962

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Microchimerism in Sjogren's syndrome. Author(s): Carlucci F, Priori R, Valesini G. Source: Rheumatology (Oxford, England). 2003 March; 42(3): 486-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12626802

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Microchimerism in Sjogren's syndrome. Author(s): Giacomelli R, Matucci-Cerinic M, Bombardieri S. Source: Annals of the Rheumatic Diseases. 2002 December; 61(12): 1039-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12429531

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Motor dominant neuropathy in Sjogren's syndrome: report of two cases. Author(s): Mochizuki H, Kamakura K, Masaki T, Hirata A, Nakamura R, Motoyoshi K. Source: Intern Med. 2002 February; 41(2): 142-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11868603

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Mucosa-associated lymphoid tissue lymphoma in Sjogren's syndrome: initial and follow-up imaging features. Author(s): Tonami H, Matoba M, Yokota H, Higashi K, Yamamoto I, Sugai S. Source: Ajr. American Journal of Roentgenology. 2002 August; 179(2): 485-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12130459

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Mucosa-associated lympoid tissue (MALT) lymphoma and primary amyloidosis in the lung in Sjogren's syndrome. Author(s): Sugai S. Source: Intern Med. 2002 April; 41(4): 251-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11993782

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Myelopathy in primary Sjogren's syndrome: diagnostic and therapeutic aspects. Author(s): Hermisson M, Klein R, Schmidt F, Weller M, Kuker W. Source: Acta Neurologica Scandinavica. 2002 June; 105(6): 450-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12027834

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Myths & facts.About Sjogren's syndrome. Author(s): McConnell EA. Source: Nursing. 2002 June; 32(6): 94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12189992

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Neurological complications of primary Sjogren's syndrome. Author(s): Lafitte C, Amoura Z, Cacoub P, Pradat-Diehl P, Picq C, Salachas F, Leger JM, Piette JC, Delattre JY. Source: Journal of Neurology. 2001 July; 248(7): 577-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11517999

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Neuropsychological, neuroimage and psychiatric aspects of primary Sjogren's syndrome. Author(s): Brito GN, Araujo GR, Papi JA. Source: Arquivos De Neuro-Psiquiatria. 2002 March; 60(1): 28-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11965405

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New approaches to the treatment of Sjogren's syndrome: soon beyond symptomatic relief? Author(s): Steinfeld S, Simonart T. Source: Dermatology (Basel, Switzerland). 2003; 207(1): 6-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12835540

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New criteria for diagnosing Sjogren's syndrome: a step forward?--or. Author(s): Manthorpe R. Source: Scand J Rheumatol Suppl. 2001; (115): 14-20; Discussion 20-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11469516

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No association between human parvovirus B19 infection and Sjogren's syndrome. Author(s): De Stefano R, Manganelli S, Frati E, Selvi E, Azzi A, Zakrzewska K, Marcolongo R. Source: Annals of the Rheumatic Diseases. 2003 January; 62(1): 86-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12480682

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No evidence of an association between the interleukin-10 promoter GCC allele and primary Sjogren's syndrome: comment on the article by Hulkkonen et al. Author(s): Lester S, Limaye V, Downie-Doyle S, Pile KD, Bardy P, Gordon TP, Rischmueller M. Source: Arthritis and Rheumatism. 2002 June; 46(6): 1694-6; Author Reply 1696-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12115207

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Non-Hodgkin's lymphoma & primary biliary cirrhosis with Sjogren's syndrome. Author(s): Hahn JS, Kim C, Min YH, Ko YW, Suh CO, Park YY. Source: Yonsei Medical Journal. 2001 April; 42(2): 258-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11371117

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Nonspecific interstitial pneumonia as pulmonary involvement of primary Sjogren's syndrome. Author(s): Yamadori I, Fujita J, Bandoh S, Tokuda M, Tanimoto Y, Kataoka M, Yamasaki Y, Yoshinouchi T, Ohtsuki Y, Ishida T. Source: Rheumatology International. 2002 July; 22(3): 89-92. Epub 2002 May 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12111081

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Novel fragments of the Sjogren's syndrome autoantigens alpha-fodrin and type 3 muscarinic acetylcholine receptor generated during cytotoxic lymphocyte granuleinduced cell death. Author(s): Nagaraju K, Cox A, Casciola-Rosen L, Rosen A. Source: Arthritis and Rheumatism. 2001 October; 44(10): 2376-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11665980

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Nutrient intake in women with primary and secondary Sjogren's syndrome. Author(s): Cermak JM, Papas AS, Sullivan RM, Dana MR, Sullivan DA. Source: European Journal of Clinical Nutrition. 2003 February; 57(2): 328-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12571668

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Observation of precorneal tear film in patients with Sjogren's syndrome. Author(s): Danjo Y, Hamano T. Source: Acta Ophthalmologica Scandinavica. 1995 December; 73(6): 501-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9019372

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Oestrogen receptors in cultured epithelial cells from salivary glands of Sjogren's syndrome patients. Author(s): Kassi E, Moutsatsou P, Sekeris CE, Moutsopoulos HM, Manoussakis MN. Source: Rheumatology (Oxford, England). 2003 September; 42(9): 1120-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12923274

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Opportunistic infection due to unexplained CD4+ lymphocytopenia and associated Sjogren's syndrome. Author(s): Schattner A, Friedman J, Bentwich Z. Source: Rheumatology (Oxford, England). 2004 January; 43(1): 111-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14681566

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Oral and ocular manifestations in Sjogren's syndrome. Author(s): Kalk WW, Mansour K, Vissink A, Spijkervet FK, Bootsma H, Kallenberg CG, Roodenburg JL, Nieuw Amerongen AV. Source: The Journal of Rheumatology. 2002 May; 29(5): 924-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12022351

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Oral and periodontal status in Sjogren's syndrome. Author(s): al-Hashimi I. Source: Tex Dent J. 2001 October; 118(10): 932-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11764624

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Oral findings in patients with primary Sjogren's syndrome and oral lichen planus--a preliminary study on the effects of bovine colostrum-containing oral hygiene products. Author(s): Pedersen AM, Andersen TL, Reibel J, Holmstrup P, Nauntofte B. Source: Clinical Oral Investigations. 2002 March; 6(1): 11-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11996158

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Oral pilocarpine for the treatment of ocular symptoms in patients with Sjogren's syndrome: a randomised 12 week controlled study. Author(s): Tsifetaki N, Kitsos G, Paschides CA, Alamanos Y, Eftaxias V, Voulgari PV, Psilas K, Drosos AA. Source: Annals of the Rheumatic Diseases. 2003 December; 62(12): 1204-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14644860

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Oral prednisolone improved acetylcholine-induced sweating in Sjogren's syndromerelated anhidrosis. Author(s): Maeda A, Yamanouchi H, Lee JB, Katayama I. Source: Clinical Rheumatology. 2000; 19(5): 396-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11055832

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Otitis externa sicca/fibrotising external otitis (FEO) as a complication of Sjogren's syndrome. Author(s): Konttinen YT, Ramsay H, Hietanen J, Sorsa T, Nordstrom D. Source: Clin Exp Rheumatol. 2000 November-December; 18(6): 746-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11138341

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Outcome measures in Sjogren's syndrome. Author(s): Asmussen KH, Bowman SJ. Source: Rheumatology (Oxford, England). 2001 October; 40(10): 1085-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11600735

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Paucity of anti-hepatitis C virus antibodies in the serum of Indian patients with Sjogren's syndrome and inflammatory myositis. Author(s): Wanchu A, Chawla Y, Dhiman RK, Sud A, Bambery P. Source: Indian J Pathol Microbiol. 2003 April; 46(2): 191-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15022906

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Physical capacity in women with primary Sjogren's syndrome: a controlled study. Author(s): Strombeck B, Ekdahl C, Manthorpe R, Jacobsson LT. Source: Arthritis and Rheumatism. 2003 October 15; 49(5): 681-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14558054

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Polymorphism of the tumour necrosis factor-alpha gene at position -308 and renal manifestations of primary Sjogren's syndrome. Author(s): Pertovaara M, Hulkkonen J, Antonen J, Holopainen P, Laippala P, Pasternack A, Hurme M. Source: Rheumatology (Oxford, England). 2004 January; 43(1): 106-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14681562

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Prevalence of antibodies against alpha-fodrin in Sjogren's syndrome: comparison of 2 sets of classification criteria. Author(s): Witte T, Matthias T, Oppermann M, Helmke K, Peter HH, Schmidt RE, Tishler M. Source: The Journal of Rheumatology. 2003 October; 30(10): 2157-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14528510

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Prevalences of herpesviruses DNA sequences in salivary gland biopsies from primary and secondary Sjogren's syndrome using degenerated consensus PCR primers. Author(s): Perrot S, Calvez V, Escande JP, Dupin N, Marcelin AG. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2003 October; 28(2): 165-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12957186

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Primary biliary cirrhosis and Sjogren's syndrome: case report. Author(s): Mandel L, Dehlinger N. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 2003 November; 61(11): 1358-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14613096

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Primary cutaneous large B-cell lymphoma of the legs in a patient with primary Sjogren's syndrome. Author(s): Selva-O'Callaghan A, Perez-Lopez J, Solans-Laque R, Lopez-Peig C, AngelBosch Gil J, Vilardell-Tarres M. Source: Clin Exp Rheumatol. 2003 September-October; 21(5): 672. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14611123

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Primary Sjogren's syndrome. Author(s): Mandel L, Sunwoo J. Source: The New York State Dental Journal. 2003 August-September; 69(7): 34-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14552024

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Primary Sjogren's syndrome: rarity in India. Author(s): Misra R, Hissaria P, Tandon V, Aggarwal A, Krishnani N, Dabadghao S. Source: J Assoc Physicians India. 2003 September; 51: 859-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14710969

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Pulmonary lesions associated with Sjogren's syndrome: radiographic and CT findings. Author(s): Matsuyama N, Ashizawa K, Okimoto T, Kadota J, Amano H, Hayashi K. Source: The British Journal of Radiology. 2003 December; 76(912): 880-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14711775

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QT dispersion in rheumatoid arthritis patients with and without Sjogren's syndrome. Author(s): Pirildar T, Sekuri C, Utuk O, Tezcan UK. Source: Clinical Rheumatology. 2003 September; 22(3): 225-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14505216

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Quality of life and nutritional studies in Sjogren's syndrome patients with xerostomia. Author(s): Hay KD, Morton RP, Wall CR. Source: N Z Dent J. 2001 December; 97(430): 128-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11887662

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Quantitative analysis of apoptosis and bcl-2 in Sjogren's syndrome. Author(s): Manganelli P, Quaini F, Andreoli AM, Lagrasta C, Pilato FP, Zuccarelli A, Monteverdi R, D'Aversa C, Olivetti G. Source: The Journal of Rheumatology. 1997 August; 24(8): 1552-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9263150

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Quantitative assessment of clinical disease status in primary Sjogren's syndrome. A cross-sectional study using a new classification model. Author(s): Asmussen K, Andersen V, Bendixen G, Bendtzen K, Prause JU, Thorn J, Wiik A, Oxholm P. Source: Scandinavian Journal of Rheumatology. 1997; 26(3): 197-205. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9225875

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Quantitative assessment of dysphagia in patients with primary and secondary Sjogren's syndrome. Author(s): Rhodus NL, Colby S, Moller K, Bereuter J. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 1995 March; 79(3): 305-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7621008

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Quantitative assessment of salivary gland inflammatory infiltration in primary Sjogren's syndrome: its relationship to different demographic, clinical and serological features of the disorder. Author(s): Gerli R, Muscat C, Giansanti M, Danieli MG, Sciuto M, Gabrielli A, Fiandra E, Vitali C. Source: British Journal of Rheumatology. 1997 September; 36(9): 969-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9376993

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Rapid improvement of osteomalacia by treatment in a case with Sjogren's syndrome, rheumatoid arthritis and renal tubular acidosis type 1. Author(s): Okada M, Suzuki K, Hidaka T, Shinohara T, Kataharada K, Matsumoto M, Takada K, Ohsuzu F. Source: Intern Med. 2001 August; 40(8): 829-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11518137

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Raynaud's phenomenon in primary Sjogren's syndrome. Prevalence and clinical characteristics in a series of 320 patients. Author(s): Garcia-Carrasco M, Siso A, Ramos-Casals M, Rosas J, de la Red G, Gil V, Lasterra S, Cervera R, Font J, Ingelmo M. Source: The Journal of Rheumatology. 2002 April; 29(4): 726-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11950013

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Recent advances in understanding molecular mechanisms in the pathogenesis and antibody profile of Sjogren's syndrome. Author(s): Jonsson R, Gordon TP, Konttinen YT. Source: Curr Rheumatol Rep. 2003 August; 5(4): 311-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14531959

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Recurrent parotitis and Sjogren's syndrome. Author(s): Munro J, Allen R. Source: Journal of Paediatrics and Child Health. 2003 March; 39(2): 158-9; Author Reply 159. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12605608

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Reproducibility of biopsy grade in Sjogren's syndrome. Author(s): Al-Hashimi I, Wright JM, Cooley CA, Nunn ME. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2001 August; 30(7): 408-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11488418

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Reversibility of histological and immunohistological abnormalities in sublabial salivary gland biopsy specimens following treatment with corticosteroids in Sjogren's syndrome. Author(s): Zandbelt MM, van den Hoogen FH, de Wilde PC, van den Berg PJ, Schneider HG, van de Putte LB. Source: Annals of the Rheumatic Diseases. 2001 May; 60(5): 511-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11302875

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Revisiting Sjogren's syndrome in the new millennium: perspectives on assessment and outcome measures. Report of a workshop held on 23 March 2000 at Oxford, UK. Author(s): Bowman SJ, Pillemer S, Jonsson R, Asmussen K, Vitali C, Manthorpe R, Sutcliffe N; Contributors to and participants at the workshop. Source: Rheumatology (Oxford, England). 2001 October; 40(10): 1180-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11600750

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Risk factors for positive minor salivary gland biopsy findings in Sjogren's syndrome and dry mouth patients. Author(s): Brennan MT, Sankar V, Leakan RA, Kleiner D, Atkinson JC, Wilkinson WE, Baum BJ, Pillemer SR. Source: Arthritis and Rheumatism. 2002 April 15; 47(2): 189-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11954013

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Risk factors for positive minor salivary gland biopsy findings in Sjogren's syndrome and dry mouth patients: something new? Author(s): Govoni M, Trotta F, Cavazzini L. Source: Arthritis and Rheumatism. 2003 February 15; 49(1): 145-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12579610

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Role of anti-calcium channel and anti-receptor autoantibodies in autonomic dysfunction in Sjogren's syndrome. Author(s): Ohlsson M, Gordon TP, Waterman SA. Source: Journal of Neuroimmunology. 2002 June; 127(1-2): 127-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12044983

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Salivary gland disease in HIV/AIDS and primary Sjogren's syndrome: analysis of collagen I distribution and histopathology in American and African patients. Author(s): McArthur CP, Africa CW, Castellani WJ, Luangjamekorn NJ, McLaughlin M, Subtil-DeOliveira A, Cobb C, Howard P, Gustafson S, Palmer D, Miranda RN. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2003 October; 32(9): 544-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12969229

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Salivary gland scintigraphy in Sjogren's syndrome and patients with sicca symptoms but without Sjogren's syndrome: the psychological profiles and predictors for salivary gland dysfunction. Author(s): Tensing EK, Nordstrom DC, Solovieva S, Schauman KO, Sippo-Tujunen I, Helve T, Natah S, Ma J, Li TF, Konttinen YT. Source: Annals of the Rheumatic Diseases. 2003 October; 62(10): 964-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12972475

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Seasonal variation in dry mouth symptoms of Sjogren's syndrome patients: a clinical follow-up study. Author(s): Rantanen II, Tenovuo JO, Pienihakkinen K, Soderling EM. Source: Clin Exp Rheumatol. 2003 September-October; 21(5): 682. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14611133

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Sialorrhoea as early oral clinical manifestation of primary Sjogren's syndrome? Author(s): Mignogna MD, Fedele S, Lo Russo L, Lo Muzio L. Source: Rheumatology (Oxford, England). 2003 September; 42(9): 1113-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12923268

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Sjogren's syndrome associated painful sensory neuropathy without sensory ataxia. Author(s): Mori K, Iijima M, Sugiura M, Koike H, Hattori N, Ito H, Hirayama M, Sobue G. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 September; 74(9): 1320-2. Erratum In: J Neurol Neurosurg Psychiatry. 2003 October; 74(10): 1447. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12933946

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Sjogren's syndrome associated with systemic lupus erythematosus: clinical and laboratory profiles and comparison with primary Sjogren's syndrome. Author(s): Manoussakis MN, Georgopoulou C, Zintzaras E, Spyropoulou M, Stavropoulou A, Skopouli FN, Moutsopoulos HM. Source: Arthritis and Rheumatism. 2004 March; 50(3): 882-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15022331

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Sjogren's syndrome in association with Crohn's disease. Author(s): Rhew EY, Ramsey-Goldman R, Buchman AL. Source: Journal of Clinical Gastroenterology. 2003 October; 37(4): 312-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14506389

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Sjogren's syndrome. Author(s): Roller C. Source: Journal of Obstetric, Gynecologic, and Neonatal Nursing : Jognn / Naacog. 2004 January-February; 33(1): 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14971546

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Sjogren's syndrome. Author(s): Rehman HU. Source: Yonsei Medical Journal. 2003 December 30; 44(6): 947-54. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14703600

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Systemic lupus erythematosus and Sjogren's syndrome: historical perspective and ongoing concerns. Author(s): Isenberg DA. Source: Arthritis and Rheumatism. 2004 March; 50(3): 681-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15022304

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The assessment of fatigue in primary Sjogren's syndrome. Author(s): Lwin CT, Bishay M, Platts RG, Booth DA, Bowman SJ. Source: Scandinavian Journal of Rheumatology. 2003; 32(1): 33-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12635943

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The effect of nasal mucosal stimulation on Schirmer tests in Sjogren's syndrome and dry eye patients. Author(s): Fujisawa A, Kitagawa K, Sugai S. Source: Advances in Experimental Medicine and Biology. 2002; 506(Pt B): 1221-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12614056

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The genetics of primary Sjogren's syndrome. Author(s): Sawalha AH, Potts R, Schmid WR, Scofield RH, Harley JB. Source: Curr Rheumatol Rep. 2003 August; 5(4): 324-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14531961

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The laryngeal and esophageal manifestations of Sjogren's syndrome. Author(s): Belafsky PC, Postma GN. Source: Curr Rheumatol Rep. 2003 August; 5(4): 297-303. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14531957

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The oral component of Sjogren's syndrome: pass the scalpel and check the water. Author(s): Wu AJ. Source: Curr Rheumatol Rep. 2003 August; 5(4): 304-10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14531958

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The role of caspase cascade on the development of primary Sjogren's syndrome. Author(s): Hayashi Y, Arakaki R, Ishimaru N. Source: J Med Invest. 2003 February; 50(1-2): 32-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12630566

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The status of lactoferrin and total iron binding capacity of human parotid saliva in Sjogren's syndrome. Author(s): Haghighat N, al-Hashimi I. Source: Clin Exp Rheumatol. 2003 July-August; 21(4): 485-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12942702

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The treatment of Sjogren's syndrome with tibolone: a case report. Author(s): Sartore A, Grimaldi E, Guaschino S. Source: American Journal of Obstetrics and Gynecology. 2003 September; 189(3): 894. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14526341

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Thyroid dysfunction in primary Sjogren's syndrome: a long-term followup study. Author(s): D'Arbonneau F, Ansart S, Le Berre R, Dueymes M, Youinou P, Pennec YL. Source: Arthritis and Rheumatism. 2003 December 15; 49(6): 804-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14673967

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Transverse myelitis occurring in association with primary biliary cirrhosis and Sjogren's syndrome. Author(s): Anantharaju A, Baluch M, Van Thiel DH. Source: Digestive Diseases and Sciences. 2003 April; 48(4): 830-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12741480

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Ultrasonography and colour doppler sonography of salivary glands in primary Sjogren's syndrome. Author(s): Carotti M, Salaffi F, Manganelli P, Argalia G. Source: Clinical Rheumatology. 2001; 20(3): 213-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11434476

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Unmasking the anti-La/SSB response in sera from patients with Sjogren's syndrome by specific blocking of anti-idiotypic antibodies to La/SSB antigenic determinants. Author(s): Routsias JG, Touloupi E, Dotsika E, Moulia A, Tsikaris V, Sakarellos C, Sakarellos-Daitsiotis M, Moutsopoulos HM, Tzioufas AG. Source: Molecular Medicine (Cambridge, Mass.). 2002 June; 8(6): 293-305. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12428060

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Up-regulated gene expression in the conjunctival epithelium of patients with Sjogren's syndrome. Author(s): Kawasaki S, Kawamoto S, Yokoi N, Connon C, Minesaki Y, Kinoshita S, Okubo K. Source: Experimental Eye Research. 2003 July; 77(1): 17-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12823984

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Up-regulation of M3-muscarinic receptors in labial salivary gland acini in primary Sjogren's syndrome. Author(s): Beroukas D, Goodfellow R, Hiscock J, Jonsson R, Gordon TP, Waterman SA. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2002 February; 82(2): 203-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11850533

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Use of cevimeline, a muscarinic M1 and M3 agonist, in the treatment of Sjogren's syndrome. Author(s): Fox RI. Source: Advances in Experimental Medicine and Biology. 2002; 506(Pt B): 1107-16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12614037

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Use of localised gene transfer to develop new treatment strategies for the salivary component of Sjogren's syndrome. Author(s): Kok MR, Baum BJ, Tak PP, Pillemer SR. Source: Annals of the Rheumatic Diseases. 2003 November; 62(11): 1038-46. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14583564

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Use of muscarinic agonists in the treatment of Sjogren's syndrome. Author(s): Fox RI, Konttinen Y, Fisher A. Source: Clinical Immunology (Orlando, Fla.). 2001 December; 101(3): 249-63. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11726216

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Use of patient age and anti-Ro/La antibody status to determine the probability of patients with systemic lupus erythematosus and sicca symptoms fulfilling criteria for secondary Sjogren's syndrome. Author(s): Prabu A, Marshall T, Gordon C, Plant T, Bawendi A, Heaton S, Jobson S, Briggs D, Bowman SJ. Source: Rheumatology (Oxford, England). 2003 January; 42(1): 189-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12509639

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Usefulness of basal and pilocarpine-stimulated salivary flow in primary Sjogren's syndrome. Correlation with clinical, immunological and histological features. Author(s): Rosas J, Ramos-Casals M, Ena J, Garcia-Carrasco M, Verdu J, Cervera R, Font J, Caballero O, Ingelmo M, Pascual E. Source: Rheumatology (Oxford, England). 2002 June; 41(6): 670-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12048294

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Usual interstitial pneumonia associated with primary Sjogren's syndrome. Author(s): Kadota J, Kusano S, Kawakami K, Morikawa T, Kohno S. Source: Chest. 1995 December; 108(6): 1756-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7497800

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Validation of the Sicca Symptoms Inventory for clinical studies of Sjogren's syndrome. Author(s): Bowman SJ, Booth DA, Platts RG, Field A, Rostron J; UK Sjogren's Interest Group. Source: The Journal of Rheumatology. 2003 June; 30(6): 1259-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12784400

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Validity of the saliva ferning test for the diagnosis of dry mouth in Sjogren's syndrome. Author(s): el-Miedany YM, el-Hady SM, el-Baddin MA. Source: Rev Rhum Engl Ed. 1999 February; 66(2): 73-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10084165

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Value of minor salivary gland biopsy in diagnosing Sjogren's syndrome. Author(s): Mahlstedt K, Ussmuller J, Donath K. Source: The Journal of Otolaryngology. 2002 October; 31(5): 299-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12512895

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Value of quantitative salivary gland scintigraphy in the early stage of Sjogren's syndrome. Author(s): Bohuslavizki KH, Brenner W, Wolf H, Sippel C, Tonshoff G, Tinnemeyer S, Clausen M, Henze E. Source: Nuclear Medicine Communications. 1995 November; 16(11): 917-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8587757

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Vascular cell adhesion molecule 1 and alpha 4 and beta 1 integrins in lymphocyte aggregates in Sjogren's syndrome and rheumatoid arthritis. Author(s): Edwards JC, Wilkinson LS, Speight P, Isenberg DA. Source: Annals of the Rheumatic Diseases. 1993 November; 52(11): 806-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7504438

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Vascular changes in major and lingual minor salivary glands in primary Sjogren's syndrome. Author(s): Takahashi H, Tezuka F, Fujita S, Okabe H. Source: Analytical Cellular Pathology : the Journal of the European Society for Analytical Cellular Pathology. 1995 December; 9(4): 243-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8616101

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VIP in salivary glands in Sjogren's syndrome. Author(s): Tornwall J, Konttinen YT, Hietanen J, Sorsa T, Hukkanen M, Uusitalo H. Source: British Journal of Rheumatology. 1995 September; 34(9): 891-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7582736

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Viral etiopathogenesis of Sjogren's syndrome: role of the hepatitis C virus. Author(s): Ramos-Casals M, Garcia-Carrasco M, Brito Zeron MP, Cervera R, Font J. Source: Autoimmunity Reviews. 2002 August; 1(4): 238-43. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12849002

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Viruses in the etiopathogenesis of Sjogren's syndrome. Author(s): Venables PJ, Rigby SP. Source: The Journal of Rheumatology. 1997 September; 24 Suppl 50: 3-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9292826

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Vth International Symposium on Sjogren's syndrome. Clinical aspects and therapy. Author(s): Fox RI. Source: Clinical Rheumatology. 1995 July; 14 Suppl 1: 17-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7493451

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What is Sjogren's syndrome and why is it important? Author(s): Talal N. Source: J Rheumatol Suppl. 2000 December; 61: 1-3. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11128697

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Whole saliva and the diagnosis of Sjogren's syndrome: an evaluation of patients who complain of dry mouth and dry eyes. Part 1: Screening tests. Author(s): Sreebny L, Zhu WX. Source: Gerodontology. 1996 July; 13(1): 35-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9452640

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Whole saliva and the diagnosis of Sjogren's syndrome: an evaluation of patients who complain of dry mouth and dry eyes. Part 2: Immunologic findings. Author(s): Sreebny L, Zhu WX. Source: Gerodontology. 1996 July; 13(1): 44-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9452641

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Widespread clonal B-cell disorder in Sjogren's syndrome predisposing to Helicobacter pylori-related gastric lymphoma. Author(s): De Vita S, Ferraccioli G, Avellini C, Sorrentino D, Dolcetti R, Di Loreto C, Bartoli E, Boiocchi M, Beltrami CA. Source: Gastroenterology. 1996 June; 110(6): 1969-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8964425

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Widespread pain and Sjogren's syndrome. Author(s): Pendarvis WT, Pillemer SR. Source: The Journal of Rheumatology. 2001 December; 28(12): 2657-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11764213

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Y chromosome microchimerism in Sjogren's syndrome. Author(s): Carlucci F, Priori R, Alessandri C, Valesini G, Stoppacciaro A. Source: Annals of the Rheumatic Diseases. 2001 November; 60(11): 1078-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11688490

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Young onset of primary Sjogren's syndrome: clinical and immunological characteristics. Author(s): Ramos-Casals M, Cervera R, Font J, Garcia-Carrasco M, Espinosa G, Reino S, Pallares L, Ingelmo M. Source: Lupus. 1998; 7(3): 202-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9607645

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CHAPTER 2. NUTRITION AND SJOGREN’S SYNDROME Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and Sjogren’s syndrome.

Finding Nutrition Studies on Sjogren’s Syndrome The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “Sjogren’s syndrome” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “Sjogren’s syndrome” (or a synonym): •

A combination of autoimmune hepatitis, sensory-dominant peripheral neuropathy, and primary Sjogren's syndrome in the same patient: a rare association. Author(s): Department of Neurology, Institute of Clinical Medicine, University of Tuskuba, Tsukuba City, Japan. Source: Hoshino, S Yoshizawa, T Hayashi, A Ohkoshi, N Tamaoka, A Shoji, S J-Med. 1999; 30(1-2): 83-92 0025-7850

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A third study on the use of orally administered anhydrous crystalline maltose for relief of dry mouth in primary Sjogren's syndrome. Author(s): Amarillo Biosciences, Incorporated, Amarillo, TX, USA. Source: Fox, P C Cummins, M J Cummins, J M J-Altern-Complement-Med. 2002 October; 8(5): 651-9 1075-5535

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Abnormal regional cerebral blood flow on 99mTc ECD brain SPECT in patients with primary Sjogren's syndrome and normal findings on brain magnetic resonance imaging. Author(s): Division of Allergy, Immunology, and Rheumatology, Changhua Christian Hospital, Changhua, Taiwan. Source: Chang, C P Shiau, Y C Wang, J J Ho, S T Kao, A Ann-Rheum-Dis. 2002 September; 61(9): 774-8 0003-4967

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Acquired hemophilia: a rare complication of Sjogren's syndrome. Author(s): Service de Medecine Interne, Hopital de la Pitie-Salpetriere, Paris, France. Source: Vignes, S Le Moing, V Meekel, P Papo, T Wechsler, B Godeau, P Clin-ExpRheumatol. 1996 Sep-October; 14(5): 559-60 0392-856X

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An investigation of interactions between the immune system and stimulus-secretion coupling in mouse submandibular acinar cells. A possible mechanism to account for reduced salivary flow rates associated with the onset of Sjogren's syndrome. Author(s): Department of Clinical Dental Sciences, The University of Liverpool, Liverpool, UK. Source: Dawson, L J Christmas, S E Smith, P M Rheumatology-(Oxford). 2000 November; 39(11): 1226-33 1462-0324

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An update on the management for the dental patient with Sjogren's syndrome and xerostomia. Author(s): Division of Oral Medicine, University of Minnesota, Minneapolis, Minnesota 55455, USA. Source: Rhodus, N L Northwest-Dent. 1999 Jul-August; 78(4): 27-34 0029-2915

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Anti-CD3 and anti-CD2-induced T-cell activation in primary Sjogren's syndrome. Author(s): Department of Internal Medicine, University of Perugia, Italy. Source: Gerli, R Bertotto, A Cernetti, C Agea, E Crupi, S Arcangeli, C Spinozzi, F Galandrini, R Rambotti, P Clin-Exp-Rheumatol. 1989 Sep-October; 7 Suppl 3S129-34 0392-856X

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Antineutrophil cytoplasmic antibody in patients with primary Sjogren's syndrome. Author(s): Second Department of Internal Medicine, Kochi Medical School, Nankoku City, Japan. [email protected] Source: Nishiya, K Chikazawa, H Hashimoto, K Miyawaki, S Clin-Rheumatol. 1999; 18(3): 268-71 0770-3198

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Beneficial effect of sodium sucrose-sulfate on the ocular surface of patients with severe KCS in primary Sjogren's syndrome. Author(s): Eye Pathology Institute, University of Copenhagen, Denmark. Source: Prause, J U Acta-Ophthalmol-(Copenh). 1991 August; 69(4): 417-21 0001-639X

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Candida albicans levels in patients with Sjogren's syndrome before and after longterm use of pilocarpine hydrochloride: a pilot study. Author(s): Division of Oral Medicine-Diagnosis, University of Minnesota, School of Dentistry, Minneapolis, USA. [email protected] Source: Rhodus, N L Liljemark, W Bloomquist, C Bereuter, J Quintessence-Int. 1998 November; 29(11): 705-10 0033-6572

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CD5-expressing B lymphocytes in the blood and salivary glands of patients with primary Sjogren's syndrome. Author(s): Department of Immunology, Brest University Medical School, France. Source: Youinou, P Mackenzie, L le Masson, G Papadopoulos, N M Jouquan, J Pennec, Y L Angelidis, P Katsikis, P Moutsopoulos, H M Lydyard, P M J-Autoimmun. 1988 April; 1(2): 185-94 0896-8411

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Characterization of mononuclear cells of inflammatory infiltrates in oral tissues. A histochemical and immunohistochemical study of labial salivary glands in Sjogren's syndrome and of oral lesions in systemic lupus erythematosus and in lichen planus. Source: Kilpi, A Proc-Finn-Dent-Soc. 1988; 84 Suppl 31-93 0355-4651

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Cholinergic-drug induced sicca syndrome in Parkinson's disease: a case report and a review of the literature. Author(s): Department of Neurology, Neurological Institute, Tokyo Women's Medical University, Japan. [email protected] Source: Hashimoto, S Sawada, T Inoue, T Yamamoto, K Iwata, M Clin-NeurolNeurosurg. 1999 December; 101(4): 268-70 0303-8467

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Clinical differences between ANA/anti-ENA positive or negative primary Sjogren's syndrome. Author(s): 4th General Medicine Division, S. Maria della Misericordia Civilian Hospital, Udine, Italy. Source: Fossaluzza, V De Vita, S Clin-Rheumatol. 1992 September; 11(3): 385-7 0770-3198

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Clinical trial of sustained-release artificial tears in keratoconjunctivitis sicca and Sjogren's syndrome. Author(s): Department of Rheumatology, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden. Source: Lindahl, G Calissendorff, B Carle, B Acta-Ophthalmol-(Copenh). 1988 February; 66(1): 9-14 0001-639X

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Current treatment modalities of oral problems of patients with Sjogren's syndrome: caries prevention. Author(s): Department of Stomatology, University of California, San Francisco 941430512, USA. Source: Newbrun, E Adv-Dent-Res. 1996 April; 10(1): 29-34 0895-9374

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Cutaneous T cell lymphoma in a patient with primary biliary cirrhosis and secondary Sjogren's syndrome. Author(s): Department of Anaesthesiology and Intensive Care Medicine, Charite University Hospital, Humboldt University, Berlin, Germany. [email protected] Source: Stroehmann, A Dorner, T Lukowsky, A Feist, E Hiepe, F Burmester, G R JRheumatol. 2002 June; 29(6): 1326-9 0315-162X

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Decay-accelerating factor (DAF, CD55)-negative T lymphocytes in the peripheral blood of Sjogren's syndrome patients. Author(s): Department of Internal Medicine, School of Medicine, Tokai University, Kanagawa, Japan. Source: Ichikawa, Y Masumoto, A Yoshida, M Yamada, C Horiki, T Hoshina, Y Uchiyama, M Takaya, M Tokai-J-Exp-Clin-Med. 1996 October; 21(3): 121-8 0385-0005

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Dry mouth symptoms of Sjogren's syndrome. Source: Anonymous Dent-Assist. 2000 Sep-October; 69(5): 22-3 1088-3886

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Effect of vitamin A treatment on immune reactivity and lipid peroxidation in patients with Sjogren's syndrome. Author(s): Department of Rheumatology, Central Hospital of Hungarian State Railways, Budapest. Source: Szocsik, K Gonzalez Cabello, R Vien, C V Mezes, M Szongoth, M Gergely, P Clin-Rheumatol. 1988 December; 7(4): 514-9 0770-3198

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Effects of calorie restriction on transforming growth factor beta 1 and proinflammatory cytokines in murine Sjogren's syndrome. Author(s): Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7874, USA. Source: Chandrasekar, B McGuff, H S Aufdermorte, T B Troyer, D A Talal, N Fernandes, G Clin-Immunol-Immunopathol. 1995 September; 76(3 Pt 1): 291-6 0090-1229

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Effects of mouthrinses with linseed extract Salinum without/with chlorhexidine on oral conditions in patients with Sjogren's syndrome. A double-blind crossover investigation. Author(s): Department of Periodontology, Centre for Oral Health Sciences, Malmo University, Sweden. [email protected] Source: Johansson, G Andersson, G Edwardsson, S Bjorn, A L Manthorpe, R Attstrom, R Gerodontology. 2001 December; 18(2): 87-94 0734-0664

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Enhanced neutrophil and eosinophil adhesion in patients with primary Sjogren's syndrome. Author(s): Department of Clinical Chemistry, University Hospital, Uppsala, Sweden. Source: Torsteinsdottir, I Gudbjornsson, B Hakansson, L Clin-Exp-Rheumatol. 1998 May-June; 16(3): 255-62 0392-856X

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Essential fatty acid and prostaglandin metabolism in Sjogren's syndrome, systemic sclerosis and rheumatoid arthritis. Source: Horrobin, D F Scand-J-Rheumatol-Suppl. 1986; 61: 242-5 0301-3847

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Experience on 60 cases of Sjogren's syndrome diagnosed and treated with traditional Chinese medicine. Source: Zhao, L J Li, Z J Huang, Y Y Ti, Z K Chen, Y J-Tradit-Chin-Med. 1989 March; 9(1): 31-4 0254-6272

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Gammalinolenic acid treatment of fatigue associated with primary Sjogren's syndrome. Author(s): Sjogren's Syndrome Research Centre, Department of Rheumatology, Malmo University Hospital, Sweden. [email protected] Source: Theander, Elke Horrobin, David F Jacobsson, Lennart T H Manthorpe, Rolf Scand-J-Rheumatol. 2002; 31(2): 72-9 0300-9742

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General pharmacological profile of the novel muscarinic receptor agonist SNI-2011, a drug for xerostomia in Sjogren's syndrome. 3rd communication: effects on respiratory and cardiovascular systems. Author(s): Research Institute of Life Science, Snow Brand Milk Products Co., Ltd., Tochigi, Japan. [email protected] Source: Arisawa, Hirohiko Fukui, Kenji Masunaga, Hiroaki Arzneimittelforschung. 2002; 52(3): 162-7 0004-4172

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Hydroxypropyl methylcellulose for the treatment of severe dry eye associated with Sjogren's syndrome. Author(s): Department of Ophthalmology, Tokyo Dental College, Ichikawa, Japan. Source: Toda, I Shinozaki, N Tsubota, K Cornea. 1996 March; 15(2): 120-8 0277-3740

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In vivo and in vitro expression of adhesion molecules by peripheral blood lymphocytes from patients with primary Sjogren's syndrome: culture-associated enhancement of LECAM-1 and CD44. Author(s): School of Pathology, University of New South Wales, Immunopathology Department, Prince Henry Hospital, Sydney, Australia. Source: Aziz, K E Wakefield, D Rheumatol-Int. 1995; 15(2): 69-74 0172-8172

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Iron and vitamin deficiencies, endocrine and immune status in patients with primary Sjogren's syndrome. Author(s): Department of Oral Medicine, The University Hospital, Linkoping, Sweden. Source: Lundstrom, I M Lindstrom, F D Oral-Dis. 2001 May; 7(3): 144-9 1354-523X

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Lectin binding studies of parotid salivary glycoproteins in Sjogren's syndrome. Author(s): Secretory & Soft Tissue Research Unit, Guy's, King's & St Thomas' School of Dentistry, London, UK. [email protected] Source: Carpenter, G H Pankhurst, C L Proctor, G B Electrophoresis. 1999 July; 20(10): 2124-32 0173-0835

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LongoVital in the treatment of Sjogren's syndrome. Author(s): Department of Oral and Maxillofacial Surgery, Bispebjerg Hospital, Copenhagen, Denmark. [email protected] Source: Pedersen, A Gerner, N Palmvang, I Hoier Madsen, M Clin-Exp-Rheumatol. 1999 Sep-October; 17(5): 533-8 0392-856X

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Natural killer cell functions are related to the cell membrane composition of essential fatty acids: differences in healthy persons and patients with primary Sjogren's syndrome. Author(s): Department of Stomatology, University of California, San Francisco. Source: Oxholm, P Pedersen, B K Horrobin, D F Clin-Exp-Rheumatol. 1992 May-June; 10(3): 229-34 0392-856X

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Oral and ocular manifestations in Sjogren's syndrome. Author(s): Department of Oral and Maxillofacial Surgery, University Hospital Groningen, The Netherlands. [email protected] Source: Kalk, W W Mansour, K Vissink, A Spijkervet, F K Bootsma, H Kallenberg, C G Roodenburg, J L Nieuw Amerongen, A V J-Rheumatol. 2002 May; 29(5): 924-30 0315162X

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Osteomalacia as a presenting manifestation of Sjogren's syndrome. Author(s): Department of Rheumatology B, El Ayachi Hospital, Rabat Teaching Hospital, Morocco. Source: Hajjaj Hassouni, N Guedira, N Lazrak, N Hassouni, F Filali, A Mansouri, A Balafrej, L Rev-Rhum-Engl-Ed. 1995 Jul-September; 62(7-8): 529-32 1169-8446

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Osteomalacia secondary to renal tubular acidosis in a patient with primary Sjogren's syndrome. Author(s): Department of Medicine, Escola Paulista de Medicina, Sao Paulo, Brazil. Source: Monte Neto, J T Sesso, R Kirsztajn, G M Da Silva, L C De Carvalho, A B Pereira, A B Clin-Exp-Rheumatol. 1991 Nov-December; 9(6): 625-7 0392-856X

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Patients with primary Sjogren's syndrome treated for two months with evening primrose oil. Source: Oxholm, P Manthorpe, R Prause, J U Horrobin, D Scand-J-Rheumatol. 1986; 15(2): 103-8 0300-9742

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Pharmacotherapy of xerostomia in primary Sjogren's syndrome. Author(s): Department of Pharmacy Practice, College of Pharmacy and Health Sciences, Drake University, Des Moines, Iowa 50311-4505, USA. [email protected] Source: Wall, G C Magarity, M L Jundt, J W Pharmacotherapy. 2002 May; 22(5): 621-9 0277-0008

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Potential therapeutic approach for the hormonal treatment of lacrimal gland dysfunction in Sjogren's syndrome. Author(s): Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts. Source: Sullivan, D A Sato, E H Clin-Immunol-Immunopathol. 1992 July; 64(1): 9-16 0090-1229

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Primary hepatic lymphoma in a patient with Sjogren's syndrome. Author(s): Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Source: Tsuruta, S Enjoji, M Nakamuta, M Makihata, T Kotoh, K Sakai, H Ando, B E Nawata, H J-Gastroenterol. 2002; 37(2): 129-32 0944-1174

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Primary Sjogren's syndrome associated with inclusion body myositis. Author(s): Department of Pathophysiology, School of Medicine, University of Athens, Greece. Source: Kanellopoulos, P Baltoyiannis, C Tzioufas, A G Rheumatology-(Oxford). 2002 April; 41(4): 440-4 1462-0324

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Rapid improvement of osteomalacia by treatment in a case with Sjogren's syndrome, rheumatoid arthritis and renal tubular acidosis type 1. Author(s): First Department of Internal Medicine, National Defense Medical College, Tokorozawa, Saitama. Source: Okada, M Suzuki, K Hidaka, T Shinohara, T Kataharada, K Matsumoto, M Takada, K Ohsuzu, F Intern-Med. 2001 August; 40(8): 829-32 0918-2918

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Salivary lactoferrin in primary Sjogren's syndrome. Author(s): Department of Immunology, Brest University Medical School, France. Source: Jezequel, N Depasse, F Jouquan, J Lelong, A Roncin, S Pare, G Pennec, Y L Youinou, P Clin-Exp-Rheumatol. 1989 Mar-April; 7(2): 123-5 0392-856X

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Severe thrombocytopenia caused by digitoxin intoxication in a patient with heart failure associated with Sjogren's syndrome. Author(s): The First Department of Internal Medicine, Kyushu University School of Medicine, Fukuoka, Japan. Source: Haro, T Shimoike, E Horiuchi, T Maruyama, T Niho, Y Jpn-Circ-J. 2000 April; 64(4): 309-11 0047-1828

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Sialic acid residues in the labial salivary glands from Sjogren's syndrome patients. Author(s): Laboratory of Histology, Faculty of Medicine, Universite Libre de Bruxelles, Belgium. Source: Penaloza, A Decaestecker, C Ribai, P Nagy, N Salmon, I Appelboom, T Danguy, A Kiss, R Steinfeld, S Clin-Exp-Rheumatol. 1999 Nov-Dec; 17(6): 713-7 0392-856X

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Sicca syndrome associated with Tropheryma whipplei intestinal infection. Author(s): Department of Experimental Medicine and Pathology, La Sapienza University, Rome, Italy. Source: Bosman, C Boldrini, R Borsetti, G Morelli, S Paglia, M G Visca, P J-ClinMicrobiol. 2002 August; 40(8): 3104-6 0095-1137

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s-IgA and cytokine levels in whole saliva of Sjogren's syndrome patients before and after oral pilocarpine hydrochloride administration: a pilot study. Author(s): Division of Oral Medicine, University of Minnesota, Minneapolis, USA. Source: Rhodus, N Dahmer, L Lindemann, K Rudney, J Mathur, A Bereuter, J Clin-OralInvestig. 1998 December; 2(4): 191-6 1432-6981

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Sjogren's syndrome and tear function parameters. Author(s): Koninklijk Nederlands Gasthuis voor Ooglijders, Utrecht, The Netherlands. Source: van Bijsterveld, O P Mackor, A J Clin-Exp-Rheumatol. 1989 Mar-April; 7(2): 1514 0392-856X

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Sjogren's syndrome. Author(s): Division of Oral Medicine, University of Minnesota, Minneapolis 55455, USA. [email protected] Source: Rhodus, N L Quintessence-Int. 1999 October; 30(10): 689-99 0033-6572

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Sjogren's syndrome: pathology, oral presentation, and dental management. Author(s): Dept. of Dental Medicine, Long Island Jewish Medical Center, New Hyde Park, New York. Source: Sciubba, J J Compendium. 1994 September; 15(9): 1084, 1086, 1088 passim; quiz 1096 0894-1009

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Suppression of tumor necrosis factor alpha-induced matrix metalloproteinase 9 production in human salivary gland acinar cells by cepharanthine occurs via downregulation of nuclear factor kappaB: a possible therapeutic agent for preventing the destruction of the acinar structure in the salivary glands of Sjogren's syndrome patients. Author(s): Department of Oral and Maxillofacial Surgery 2, Tokushima University School of Dentistry, 3 Kuramoto-cho, Tokushima 770-8504, Japan. [email protected] Source: Azuma, Masayuki Aota, Keiko Tamatani, Tetsuya Motegi, Katsumi Yamashita, Tsuyoshi Ashida, Yuki Hayashi, Yoshio Sato, Mitsunobu Arthritis-Rheum. 2002 June; 46(6): 1585-94 0004-3591

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Tear fluid analysis in primary Sjogren's syndrome. Author(s): Department of Rheumatology, Dr Daniel den Hoed Clinic, Rotterdam, The Netherlands. Source: Markusse, H M van Haeringen, N J Swaak, A J Hogeweg, M de Jong, P T ClinExp-Rheumatol. 1993 Mar-April; 11(2): 175-8 0392-856X

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Tear function parameters in keratoconjunctivitis sicca with and without the association of Sjogren's syndrome. Author(s): Koninklijk Nederlands Gasthuis voor Ooglijders, Utrecht, The Netherlands.

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Source: Mackor, A J van Bijsterveld, O P Ophthalmologica. 1988; 196(4): 169-74 00303755 •

Test and symptoms in keratoconjunctivitis sicca and their correlation. Author(s): Department of Ophthalmology, Rigshospitalet and Eye Pathology Institute, University of Copenhagen, Denmark. Source: Bjerrum, K B Acta-Ophthalmol-Scand. 1996 October; 74(5): 436-41 1395-3907

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The diagnostic value of salivary fluid levels of beta 2-microglobulin, lysozyme and lactoferrin for primary Sjogren's syndrome. Author(s): Department of Rheumatology, Dr. Daniel Den Hoed Clinic, Rotterdam, The Netherlands. Source: Markusse, H M Otten, H G Vroom, T M Smeets, T J Fokkens, N Breedveld, F C Clin-Rheumatol. 1992 December; 11(4): 521-5 0770-3198

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The effect of parotid salivary flow rate on the levels of salivary antimicrobial proteins in patients with Sjogren's syndrome. Author(s): Baylor College of Dentistry, Texas A&M University System, Dallas 75246, USA. Source: Zipp, M M Yasbin, L al Hashimi, I Quintessence-Int. 1999 October; 30(10): 700-5 0033-6572

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The lactoferrin tear test in the diagnosis of Sjogren's syndrome. Author(s): Institute of Ophthalmology, University of Roma La Sapienza, Italy. Source: Da Dalt, S Moncada, A Priori, R Valesini, G Pivetti Pezzi, P Eur-J-Ophthalmol. 1996 Jul-September; 6(3): 284-6 1120-6721

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The occurrence of renal involvement in primary Sjogren's syndrome: a study of 78 patients. Author(s): Department of Internal Medicine, Tampere University Hospital, University of Tampere, Tampere, Finland. Source: Pertovaara, M Korpela, M Kouri, T Pasternack, A Rheumatology-(Oxford). 1999 November; 38(11): 1113-20 1462-0324

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The ratio of albumin to lactoferrin in tear fluid as a diagnostic tool in primary Sjogren's syndrome. Author(s): Department of Ophthalmology, Rigshospitalet, Copenhagen, Denmark. Source: Bjerrum, K B Acta-Ophthalmol-Scand. 1997 October; 75(5): 507-11 1395-3907

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The treatment of Sjogren's syndrome patients with pilocarpine-tablets. Author(s): Jefferson Sjogren's Syndrome Center, Division of Rheumatology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA. [email protected] Source: Vivino, F B Scand-J-Rheumatol-Suppl. 2001; (115): 1-9; discussion 9-13 0301-3847

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Tolerability and efficacy of oral chrysotherapy in patients with Sjogren's syndrome secondary to rheumatoid arthritis (SS-RA). Author(s): Institute of Internal Medicine, University of Calgary, Italy. Source: Mathieu, A Pala, R Nurchis, P Contu, L Clin-Rheumatol. 1989 September; 8(3): 413-6 0770-3198

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Treatment of depression with fluoxetine in corticosteroid-dependent central nervous system Sjogren's syndrome. Author(s): Department of Psychiatry, Bellevue Hospital, New York. Source: Wyszynski, A A Wyszynski, B Psychosomatics. 1993 Mar-April; 34(2): 173-7 0033-3182

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Treatment of primary Sjogren's syndrome with D-penicillamine: a pilot study. Author(s): Department of Rheumatology, Sint Antonius Hospital, Koekoekslaan 1, 3430 EM Nieuwegein, the Netherlands. Source: ter Borg, E J Haanen, H C Haas, F J Bistervels, J H Huisman, F W Kerckhaert, J A Kallenberg, C G Neth-J-Med. 2002 November; 60(10): 402-6 0300-2977

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Use of muscarinic agonists in the treatment of Sjogren's syndrome. Author(s): Allergy and Rheumatology Clinic, Scripps Memorial Hospital and Research Foundation, La Jolla, California 92037, USA. [email protected] Source: Fox, R I Konttinen, Y Fisher, A Clin-Immunol. 2001 December; 101(3): 249-63 1521-6616

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Vascular changes in major and lingual minor salivary glands in primary Sjogren's syndrome. Author(s): Department of Oral Pathology, Nagasaki University School of Dentistry, Japan. Source: Takahashi, H Tezuka, F Fujita, S Okabe, H Anal-Cell-Pathol. 1995 December; 9(4): 243-56 0921-8912

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VTH International Symposium on Sjogren's syndrome. Clinical aspects and therapy. Author(s): Division of Rheumatology, MS-212 Scripps Clinic and Research Foundation 10, La Jolla, CA 92037, USA. Source: Fox, R I Clin-Rheumatol. 1995 July; 14 Suppl 117-9 0770-3198

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

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Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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CHAPTER 3. CLINICAL TRIALS AND SJOGREN’S SYNDROME Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning Sjogren’s syndrome.

Recent Trials on Sjogren’s Syndrome The following is a list of recent trials dedicated to Sjogren’s syndrome.8 Further information on a trial is available at the Web site indicated. •

Evaluation of Salivary Gland Dysfunction Condition(s): Sjogren's Syndrome; Xerostomia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Dental and Craniofacial Research (NIDCR) Purpose - Excerpt: This study will evaluate patients with complaints of dry mouth to determine the cause and severity of their salivary gland dysfunction and their possible eligibility for other NIDCR protocols. Salivary gland secretions have antibacterial, lubricatory, remineralizing, digestive, buffering and cleansing properties. Impaired function of these glands can cause an increase in tooth decay; a variety of oral hard and soft tissue changes, with painful, burning, or ulcerated oral mucosal; problems chewing, swallowing, and speaking; and diminished taste and smell. Patients with dry mouth complaints suggestive of salivary gland dysfunction may be eligible for this study. In addition, patients with recent onset of arthritis may enroll. Patients with arthritis are at risk for developing a disorder called Sjogren's syndrome, in which the glands that produce saliva may be damaged. Participants will have a complete medical and dental history. Saliva samples will be collected from the major salivary glands, which are located in the cheeks and under the jaw. Several blood samples will also be drawn for tests. Some patients will have a biopsy of the minor salivary glands, usually from the lower lip, to confirm or rule out the diagnosis of Sjogren's syndrome and determine the extent of changes in the salivary glands. The ability to taste and smell may also be

8

These are listed at www.ClinicalTrials.gov.

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evaluated, and patients may have an ultrasound examination of their swallowing function. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001196 •

Natural History of Salivary Gland Dysfunction and Sjogren's Syndrome Condition(s): Lymphoma; Salivary Gland Disease; Sjogren's Syndrome; Xerostomia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Dental and Craniofacial Research (NIDCR) Purpose - Excerpt: This study will follow patients with salivary gland dysfunction to identify the long-term course of this disorder and its effects on the mouth, oral function, and overall health. Saliva is important in maintaining oral health and comfort. It moistens the mouth, lubricates food for easier swallowing, provides enzymes needed to begin the digestive process and promotes repair and cleansing of soft tissues of the mouth. Decreased salivary production or changes in salivary composition may affect oral and systemic health and cause an increase in tooth decay. Patients 4 years of age and older with dry mouth symptoms and a diagnosis of primary, secondary or incomplete Sjogren's syndrome or salivary gland dysfunction due to radiation may be eligible for this study. Candidates will be screened with a complete medical and dental history and blood and saliva tests. Some patients will have a biopsy of the minor salivary glands, usually from the lower lip, to confirm or rule out the diagnosis of Sjogren's syndrome and determine the extent of changes in the salivary glands. (A biopsy is the surgical removal of a small piece of tissue for laboratory examination.) The ability to taste and smell may also be evaluated, and patients may have an ultrasound examination of their swallowing function. Participants will have a general oral examination of the teeth and soft tissues of the mouth, general physical examination, eye examination and blood tests and will fill out a questionnaire on oral health and function. In addition, they will have the following tests and procedures: - Identification of possible fungal infection - Patients rinse their mouth with 2 teaspoons of a salt-water solution and spit it in a sterile container for laboratory examination. If a fungal infection is detected, treatment will be offered. - Unstimulated salivary function assessment Saliva production is measured by collecting saliva samples through small suction cups connected to collection tubes over the salivary gland ducts in the mouth. - Stimulated salivary function assessment - A sour-tasting liquid (2% citric acid) is applied to the top and sides of the tongue at 30-second intervals to stimulation saliva production while saliva is collected using the procedure described above. - Identification of markers of precancerous lesions - The salivary gland biopsy done at the screening evaluation (or from outside sources) is examined for markers of precancerous lesions, as about 5 percent of patients with Sjogren's syndrome develop a tumor called Non-Hodgkin's lymphoma. In some cases, the minor salivary glands may be re-biopsied a few years after the screening biopsy. Patients will be followed once a year with a comprehensive history and physical examination, eye examination, full oral examination, salivary function assessment and questionnaires about signs and symptoms of salivary gland dysfunction. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001852

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Six month clinical research study for patients with moderate or severe dry eye syndrome Condition(s): Keratoconjunctivitis Sicca; Sjogren's Syndrome; Lupus Erythematosus, Systemic; Arthritis, Rheumatoid; Scleroderma, Systemic Study Status: This study is currently recruiting patients. Sponsor(s): Allergan Purpose - Excerpt: A six-month clinical research trial to evaluate the effectiveness of an investigational medication for the treatment of dry eye syndrome in patients that have been diagnosed with moderate to severe dry eye syndrome, an autoimmune disorder AND/OR females 65 years of age or older. Phase(s): Phase III Study Type: Interventional Contact(s): Rheumatology Research International 1-888-297-4247 [email protected] Web Site: http://clinicaltrials.gov/ct/show/NCT00025818

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The Research Registry for Neonatal Lupus Condition(s): Neonatal lupus; Systemic Lupus Erythematosus; Sjogren's Syndrome; Congenital heart block Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: Women with lupus and other related disorders produce certain antibodies in the blood. Some women have these antibodies even if they have not yet developed symptoms of lupus or Sjogren's syndrome. When these women become pregnant, they may pass the antibodies to their infants. The infants may then develop a disease called neonatal lupus. The symptoms of neonatal lupus include an abnormally slow heart beat (heart block) and a skin rash. This registry collects information on women and infants affected by neonatal lupus as well as other family members who may be healthy. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00074373

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Potential of Transplanted Stem Cells to Mature into Salivary Gland and Cheek Cells Condition(s): Graft vs Host Disease; Sjogren's Syndrome Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Dental and Craniofacial Research (NIDCR) Purpose - Excerpt: This study will examine whether transplanted stem cells can turn into salivary gland cells in stem cell recipients. If so, stem cells might be used to restore salivary gland function in patients with Sjogren's syndrome and other causes of dry mouth. People with severe dry mouth may develop difficulty swallowing, severe tooth decay, infections of the mouth and pharynx, and mouth sores. Female patients 18 years of age and older who are enrolled in the National Heart, Lung and Blood Institute's protocol 97-H-009 or 97-H-0202 and who have received a stem cell transplant from a

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male donor may be eligible for this study. Five patients with graft-versus host disease (GVHD) and five without GVHD will be included. GVHD is a transplantation reaction in which the donor's cells mount an immune response against the recipient's tissues. Patients with chronic GVHD have mouth ulcerations and dry mouth similar to that of patients with Sjogren's syndrome. Five healthy female volunteers will also be enrolled. Participants will have a medical and dental history. Then, cells will be collected from the inside of the cheek (buccal cell scraping) and from the salivary glands (labial gland biopsy) as described below: Buccal cell scraping - Cells are collected from the inside of the cheek by wiping for 5 seconds with a plastic brush. Labial glands biopsy - The lower lip will be numbed and a small incision will be made on the inside of the lower lip. Six small salivary glands in the lower lip will be removed and the incision will be closed with four stitches. Cells collected from these procedures will be examined to see if donated stem cells turned into salivary gland or cheek cells. Patients will return to the clinic 5 to 10 days after the biopsy to have the stitches removed and assess healing. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00023491 •

DHEA Treatment for Sjogren's Syndrome Condition(s): Lacrimal Apparatus Disease; Salivary Gland Disease; Sjogren's Syndrome; Xerostomia Study Status: This study is completed. Sponsor(s): National Institute of Dental and Craniofacial Research (NIDCR) Purpose - Excerpt: This study will evaluate the effectiveness of the male hormone dehydroepiandrosterone (DHEA) in treating Sjogren's syndrome. This autoimmune disorder, in which the immune system attacks the salivary glands and tear glands, affects primarily women. Patients' eyes and mouth become drier over time, and can lead to problems such as serious tooth decay and eye irritations. Sex hormones seem to influence the immune response and may help decrease disease severity. DHEA has benefited some patients with two other autoimmune diseases, rheumatoid arthritis and systemic lupus erythematosus. Women 18 to 75 years of age with Sjogren's syndrome may be eligible for this 7-month study. At the initial visit, candidates will have a physical examination, routine blood and urine tests and eye and dental examinations, including a test to measure saliva production for screening purposes and to establish baseline values for participants. Those enrolled in the study will be randomly assigned to take either DHEA or placebo (look-alike tablet with no active ingredient) once a day for 6 months and will be monitored with follow-up visits at months 1, 3, 6 and 7. Physical examination, blood tests and urinalysis will be repeated at months 1, 3, 6 and 7; saliva will be collected at months 3, 6 and 7; and eyes will be examined at 3 and 6 months. Because hormone changes may have both physical and emotional effects, patients will be asked questions about their mood, symptoms and side effects of treatment. It is not known if Sjogren's syndrome is associated with osteoporosis (bone thinning), but since this condition occurs in other autoimmune disorders, patient's bone density will be measured at the first visit, and blood drawn at 3 and 6 months will be tested for various substances associated with changes in bone density. A 24-hour urine collection at the first visit and later urine tests will also be tested for substances associated with bone thinning. Phase(s): Phase II

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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001598 •

Etanercept Therapy for Sjogren's Syndrome Condition(s): Sjogren's Syndrome Study Status: This study is completed. Sponsor(s): National Institute of Dental and Craniofacial Research (NIDCR) Purpose - Excerpt: This study will test the effectiveness of etanercept (Enbrel) for treating Sjogren's syndrome-an autoimmune disease that affects the secreting glands. (In autoimmune diseases, the immune system attacks the body's own tissues.) Reduced lacrimal (tear) gland function causes dry eyes with a scratchy sensation, and, in severe cases, vision be may impaired. Reduced salivary gland function causes dry mouth, resulting in greatly increased tooth decay. Dry mouth also makes chewing and swallowing difficult, which may lead to nutrition deficiencies. Sjogren's syndrome can also cause dryness of the skin and of mucous membranes in the nose, throat, airways, and vagina. Patients with Sjogren's syndrome who have had oral and eye examinations under NIDCR's protocol 84-D-0056 may participate in this study. Participants will be randomly assigned to receive either etanercept or placebo (an inactive look-alike substance) by injection under the skin twice a week for 3 months. Patients will be seen for evaluation before treatment begins (baseline) and again at 1, 3, and 4 months. The baseline and 3-month visits include a physical examination, eye examination, saliva collection from salivary glands, blood tests, and evaluation for changes in symptoms and treatment side effects. The 1- and 4-month visits include saliva collection, blood tests, and review of symptoms and treatment side effects. In addition, blood will be drawn every 2 weeks for safety monitoring. Patients will also be surveyed weekly (by telephone or during the clinic visit) about symptoms and treatment side effects. The Food and Drug Administration has approved Enbrel for treating certain forms of arthritis, which, like Sjogren's syndrome, are autoimmune disorders of the connective tissue. Laboratory studies also indicate that etanercept may be an effective treatment for Sjogren's syndrome. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001954

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Pilot Study of Thalidomide to Treat Sjogren's Syndrome Condition(s): Sjogren's Syndrome; Xerostomia Study Status: This study is completed. Sponsor(s): National Institute of Dental and Craniofacial Research (NIDCR) Purpose - Excerpt: This study will evaluate the safety and effectiveness of thalidomide in treating Sjogren's syndrome. In this autoimmune disease, the immune system attacks the body's tear glands and salivary glands, causing dry mouth and dry eyes. Thalidomide has shown promise in treating other autoimmune disorders, such as rheumatoid arthritis and systemic lupus erythematosus. Women with Sjogren's syndrome who have dry eyes and dry mouth may be eligible for this study. Women of

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childbearing potential will not be considered for participation because of severe birth defects associated with thalidomide. Also, since Sjogren's syndrome affects many fewer men than women, men are excluded from this pilot study because they would be too few in number to assess as a separate group. Candidates will be screened with a medical history, physical examination, blood and urine tests, electrocardiogram, chest X-ray and pregnancy test. Tests will also be done to measure the conduction of electrical impulses along the nerves and to evaluate dryness of the eyes. Participants will be randomly assigned to take either thalidomide or a placebo (look-alike pill with no active ingredient). The thalidomide dosage will be increased gradually from a starting dose of 50 Mg. up to 300 Mg., depending on side effects. Women of childbearing age who have had a tubal ligation or longstanding infertility will have a pregnancy test every 2 or 4 weeks. Participants will come to the clinic at the first study visit and again at weeks 4, 8 and 12 for some or all of the following procedures: - Patient assessment of dry mouth (rated on a scale from "worst ever" to "best ever" - Patient assessment of dry eyes (rated on a scale from "worst ever" to "best ever" - Patient health questionnaire and disease assessment rating - Saliva collection - Rose-Bengal or other dye tests for dryness examination of the eyes under a bright light following administration of drops containing a dye - Schirmer's I test for dryness - placement of a thin rectangular strip of filter paper in the eye following administration of anesthetic drops - Blood tests to measure blood cell counts and levels of various immune substances in the blood, and to evaluate liver and kidney function - Urine tests to evaluate kidney function - Nerve conduction tests - measurement of the speed with which nerves conduct electrical impulses. Two nerves in the arm and one nerve in the leg will be tested. Participants will also be contacted by telephone every week to report any side effects. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001599 •

Study of INS365 Ophthalmic Solution in a Controlled Adverse Environment in Patients with Dry Eye Condition(s): Keratoconjunctivitis Sicca Study Status: This study is completed. Sponsor(s): Inspire Pharmaceuticals Purpose - Excerpt: Comparative efficacy trial of INS365 Ophthalmic Solution and placebo in patients with dry eye. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00037661

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The Functioning of Immune and Hormonal Systems in Patients with Sjogren's Syndrome and in Healthy Volunteers Condition(s): Sjogren's Syndrome Study Status: This study is completed. Sponsor(s): National Institute of Dental and Craniofacial Research (NIDCR)

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Purpose - Excerpt: This study aims to learn more about how the immune and hormonal systems function in patients with Sjogren's syndrome, a disease in which the immune system does not function properly. Adult nonpregnant females are invited to participate. Oral contraceptives may not be taken for 6 weeks before and during this study, so another form of birth control must be used, such as abstinence. There will be two visits. At the first visit, a medical history and physical examination will be conducted, and blood and urine tests will be done. The total amount of blood drawn will be 10 tablespoons. This visit will last 3 hours. At the second visit, participants will have an oral glucose tolerance test. To prepare for it, they must be on a special diet for 3 days beforehand and keep a diary of eating, sleeping, and physical activities for those 3 days. A urine sample will be taken at the beginning of the visit. Subjects must then drink a very sweet carbonated cola. A small plastic tube will be placed into an arm vein. Blood will be drawn through this tube eight times over 3 hours. The total amount of blood drawn will be 17 tablespoons. Only minor inconveniences are anticipated as a result of participating in this study. Risks from blood tests include soreness, bruising, and minor infection at the puncture site, and dizziness. The oral glucose tolerance test may cause temporary stomach bloating, headache, nausea, and vomiting. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001953 •

Treatment of Dry Eye Syndrome with Cyclosporin A Eye Drops Condition(s): Keratoconjunctivitis Sicca; Sjogren's Syndrome Study Status: This study is completed. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: This study will examine whether cyclosporin A eye drops alleviate dry eye syndrome, a disorder of tear deficiency or excessive tear evaporation. The condition damages the surface of the eye and causes discomfort. Age-related dry eye syndrome may result from a problem with the immune system in which cells called lymphocytes infiltrate the tear glands and cause a chronic, progressive inflammatory process. Previous studies suggest that cyclosporin A may increase tear production or decrease inflammation on the surface of the eye, or both, improving dry eye symptoms. Patients in the study will undergo a complete eye examination, and a small tear sample will be collected to study tear consistency and composition. A small amount of conjunctiva (the clear, thin covering of the eye lining the eyelids and eyeball) will be removed to study substances in it that might provide information on what causes dry eye. A blood sample also will be taken to look for antibodies found in patients with Sjogren's syndrome, a disorder characterized by dryness of the mouth, eyes and other mucous membranes. Patients will also fill out forms providing information on the extent to which their dry eyes bother them. Patients will be randomly divided into two treatment groups: one will take a cyclosporin 0.1% eye drop emulsion; the other will take the emulsion vehicle alone-that is, the same drops but without the active ingredient cyclosporin. Both groups will take one drop in each eye 4 times a day for 2 months. Neither the patients nor the doctors will know which patients are receiving which medication until the study ends. All patients will also be given artificial teardrops to use for comfort if needed. Phase(s): Phase II Study Type: Interventional

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001731

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “Sjogren’s syndrome” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 4. BOOKS ON SJOGREN’S SYNDROME Overview This chapter provides bibliographic book references relating to Sjogren’s syndrome. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on Sjogren’s syndrome include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “Sjogren’s syndrome” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on Sjogren’s syndrome: •

Sjogren's Syndrome Source: Torrance, CA: Homestead Schools, Inc. 2001. 101 p. Contact: Available from Homestead Schools, Inc. 23844 Hawthorne Boulevard, Suite 200, Torrance, CA 90505. (310) 791-9975. Fax (310) 791-0135. E-mail: [email protected]. Website: www.homesteadschools.com. PRICE: $48.00 plus shipping and handling. Course No. 6590. Summary: Sjogren's syndrome is a chronic disorder of unknown cause characterized by a particular form of dry mouth (xerostomia) and dry eyes. This continuing education program for dentists focuses on Sjogren's syndrome (SS). Topics include the symptoms of SS and how to distinguish between primary and secondary SS; autoimmune response systems and the role of hereditary and environmental factors in causing SS; other causes of dry eyes and xerostomia; the salivary and nonsalivary causes of xerostomia;

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treatment approaches for patients with SS; the advantages and side effects of certain medications used by SS patients; treatment alternatives to oral Candida mucositis, oral dryness, and tooth decay for patients with SS; other symptoms of SS and their treatments, including vaginal dryness, fatigue, depression, and heartburn; and the use of pilocarpine tables for the treatment of xerostomia and dry eye symptoms in patients with SS. The document concludes with a posttest with which readers can qualify for continuing education credit, a glossary of terms, and an appendix of product and manufacturer information. The document is illustrated with numerous black and white photographs. 4 figures. 14 tables. 62 figures.

Chapters on Sjogren’s Syndrome In order to find chapters that specifically relate to Sjogren’s syndrome, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and Sjogren’s syndrome using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “Sjogren’s syndrome” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on Sjogren’s syndrome: •

Salivary Gland Diseases Source: in Eisen, D. and Lynch, D.P. Mouth: Diagnosis and Treatment. St. Louis, MO: Mosby, Inc. 1998. p. 255-276. Contact: Available from Harcourt Health Sciences. Book Order Fulfillment Department, 11830 Westline Industrial Drive, St. Louis, MO 63146-9988. Website: www.mosby.com. PRICE: $79.95 plus shipping and handling. ISBN: 0815131054. Summary: This chapter on salivary gland diseases is from a textbook on the mouth that offers information to primary care physicians and to many specialists in medicine and dentistry. The authors begin by discussing nonneoplastic salivary gland diseases, including sialadenosis (enlargement of the salivary glands), benign lymphoepithelial lesion and Sjogren's syndrome, adenomatoid hyperplasia (overgrowth) of the salivary glands, mucocele (mucus retention phenomenon), ranula, mucus retention cyst (salivary duct cyst), sialolithiasis (salivary gland stone), sialadenitis (infectious and noninfectious inflammation of the salivary glands), cheilitis glandularis, sialorrhea (ptyalism, or increased salivation), xerostomia (dry mouth), and necrotizing sialometaplasia. The section on neoplastic salivary gland diseases covers benign salivary gland neoplasms, malignant salivary gland neoplasms, adenoid cystic carcinoma (cylindroma), malignant mixed tumor, acinic cell carcinoma, and polymorphous low grade adenocarcinoma (terminal duct carcinoma). For each condition, the authors describe symptoms, identification, complications, and treatment. The chapter is illustrated with numerous full color photographs of the conditions under discussion. 21 figures. 139 references.

•

Diagnosis and Treatment of Salivary Gland Disease Source: in Kwon, P.H. and Laskin, D.M. Clinician's Manual of Oral and Maxillofacial Surgery. Chicago, IL: Quintessence Publishing Co, Inc. 2001. p. 393-406.

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Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail: [email protected]. Website: www.quintpub.com. PRICE: $58.00 plus shipping and handling. ISBN: 0867153962. Summary: This chapter on the diagnosis and treatment of salivary gland disease is from a spiral-bound handbook that offers quick reference information to the oral and maxillofacial surgeon. The outline and chart-based format is designed to offer quick access to information that may be needed in situations that do not allow time for a leisurely perusal of textbooks and journals. The introduction of the chapter notes that the clinical history is one of the most important tools in establishing a diagnosis in patients presenting with suspected salivary gland disorders. Pertinent questions should aid in the characterization of any mass (extent, duration, pain, rate of growth), and provide information about consistency of the saliva, taste characteristics, and the possible presence of other areas of involvement, such as joints, eyes, and organs including the pancreas, liver, or lungs. The chapter then covers the physical examination; the preoperative workup, including sialography, computed tomography (CT scan), magnetic resonance imaging (MRI), ultrasound, and biopsy; and specific conditions, including nonspecific inflammatory disorders, specific inflammatory disorders (such as tuberculosis, mumps, or sarcoidosis), immunologic inflammatory disorders (notably Sjogren's syndrome), noninflammatory disorders, obstructive disorders (including sialolithiasis or stones), mucus retention phenomenon, trauma, benign tumors, malignant tumors, salivary gland disease in children, and complications of trauma and surgery. 1 table.

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CHAPTER 5. PERIODICALS AND NEWS ON SJOGREN’S SYNDROME Overview In this chapter, we suggest a number of news sources and present various periodicals that cover Sjogren’s syndrome.

News Services and Press Releases One of the simplest ways of tracking press releases on Sjogren’s syndrome is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “Sjogren’s syndrome” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to Sjogren’s syndrome. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “Sjogren’s syndrome” (or synonyms). The following was recently listed in this archive for Sjogren’s syndrome: •

Maternal-fetal microchimerism seen in Sjogren's syndrome lesions Source: Reuters Medical News Date: December 13, 2002

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Fibromyalgia not linked to fatigue in Sjogren's syndrome Source: Reuters Medical News Date: November 14, 2000

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Sjogren's syndrome usually does not lead to pulmonary disease Source: Reuters Medical News Date: September 25, 2000

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Neurotransmission-inhibiting autoantibodies identified in Sjogren's syndrome Source: Reuters Industry Breifing Date: July 26, 2000

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Airway responsiveness differs in asthma and Sjogren's syndrome Source: Reuters Medical News Date: April 18, 2000

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Amarillo's Sjogren's syndrome drug progresses in late-stage studies Source: Reuters Industry Breifing Date: April 10, 2000

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Public largely unaware of Sjogren's syndrome Source: Reuters Health eLine Date: March 29, 1999

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Canada Approves Pilocarpine For Symptoms Of Sjogren's Syndrome Source: Reuters Medical News Date: August 19, 1997

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Retrovirus Detected In Salivary Glands Of Sjogren's Syndrome Patients Source: Reuters Medical News Date: April 15, 1997

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Amarillo Biosciences Starts Phase II Trial Of Drug For Treatment Of Sjogren's Syndrome Source: Reuters Medical News Date: December 04, 1996 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name.

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Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “Sjogren’s syndrome” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “Sjogren’s syndrome” (or synonyms). If you know the name of a company that is relevant to Sjogren’s syndrome, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “Sjogren’s syndrome” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “Sjogren’s syndrome” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on Sjogren’s syndrome: •

Sicca Syndrome and Sjogren's Syndrome in Lupus Source: Lupus News. 23(1): 14-18. Spring 2003. Contact: Available from Lupus Foundation of America, Inc. P.O. Box 932615, Atlanta, GA 31193-2615. (866) 484-3532. Fax: (770) 442-9724. Email: [email protected]. Website: www.lupus.org. Summary: Persistent dryness of the eyes and mouth (sicca syndrome) is quite common in people with systemic lupus erythematosus (SLE). In some cases, this dryness is caused by an autoimmune reaction called Sjogren's syndrome. Regardless of the cause,

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medical treatments, along with patient education, can ease this source of discomfort and prevent potential health problems. This article presents a case report of a woman with SLE, then discusses terminology, prevalence of sicca syndrome, diagnostic considerations, complications, patient care management, mouth care, eye care, care for other local complications, and systemic therapies. One sidebar lists the Revised International Classification Criteria for Sjogren's Syndrome; another considers the use of laser vision correction operations from the perspective of determining candidacy for these operations. 2 figures. 8 references. •

Sjogren's Syndrome and the Gastrointestinal Tract Source: Moisture Seekers Newsletter. 17(2): 1, 4-5. March 1999. Contact: Available from Sjogren's Syndrome Foundation, Inc. 8120 Woodmont Avenue, Suite 530, Bethesda, MD 20814-1437. (301) 718-0300 or (800) 475-6473. Fax (301) 718-0322. Website: www.sjogrens.org. Summary: This article on Sjogren's syndrome (SS) and the gastrointestinal tract is from a patient education newsletter for people with SS. The author outlines the areas where the gastroenterologist may play a role in caring for the person with SS, such as dealing with swallowing difficulties, dyspepsia (indigestion), diarrhea, and jaundice (usually due to primary biliary cirrhosis, or scarring). Difficulty in swallowing is usually due to the lack of saliva associated with SS, but occasionally it may be due to a blockage (postcricoid web) or a weakness of the muscle contractions involved in swallowing. In addition, those patients with SS are vulnerable to acid reflux, which causes heartburn symptoms. Children with SS are prone to achalasia, a type of muscle problem involving the lower esophageal sphincter. Dyspepsia (indigestion) is relatively common in patients with SS, as is inflammation of the stomach (gastritis). The author briefly discusses the role of the bacterium Helicobacter pylori in gastritis. There are at least two diseases associated with SS and diarrhea: chronic pancreatitis and celiac disease (gluten intolerance). The author notes that the link between SS and gastroenterological conditions is often via abnormal autoantibodies.

•

Oral Aspects of Sjogren's Syndrome Source: Moisture Seekers Newsletter. 14(1): 1,4. February 1996. Contact: Available from Sjogren's Syndrome Foundation, Inc. 8120 Woodmont Avenue, Suite 530, Bethesda MD 20814-1437. (301) 718-0300 or (800) 475-6473. Fax (301) 718-0322. Website: www.sjogrens.org. Summary: This newsletter article familiarizes readers with the oral aspects of Sjogren syndrome (SS). Topics discussed include the role of saliva, the clinical signs and symptoms of dry mouth (xerostomia), and the management of xerostomia. The management of xerostomia, in most cases, is palliative and directed to relieving discomfort. Increasing fluid intake is recommended, as is using salivary stimulants, such as sugarless chewing gum and sugarless candies, to stimulate the salivary output. The author concludes that frequent dental consultations and topical fluoride applications are necessary for the management of dental problems. 3 tables.

•

Eating Your Way to Better Health: How Important Is Nutrition for Sjogren's Syndrome? Source: Moisture Seekers Newsletter. p. 1,3. Winter 1999.

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Contact: Available from Sjogren's Syndrome Foundation, Inc. 8120 Woodmont Avenue, Suite 530, Bethesda MD 20814-1437. (301) 718-0300 or (800) 475-6473. Fax (301) 718-0322. Website: www.sjogrens.org. Summary: This patient newsletter article considers the role of nutrition for patients with Sjogren's syndrome. The article is a reprint of a chapter from a book entitled Power Nutrition for Your Chronic Illness (Warner Books, 1998). The author first reviews the negative impact of Sjogren's syndrome on nutrition, including problems with eating (due to lack of saliva), tooth decay and earlier tooth loss, malabsorption of some nutrients, and the need for increased nutrient intake to recover from mouth infections, which are a common concern for people with Sjogren's syndrome. The author then focuses on Sjorgren's syndrome as an autoimmune disease and offers strategies to boost the immune system, based on general nutrition. The list of nutrients important to the immune system is quite long, which is why it is so important to eat a varied diet. The author cautions against overdosing on vitamins and minerals. Two final sections offer suggestions for coping with the lack of saliva that is typical in patients with Sjogren's syndrome and suggestions that may help counter nutrient malabsorption.

Academic Periodicals covering Sjogren’s Syndrome Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to Sjogren’s syndrome. In addition to these sources, you can search for articles covering Sjogren’s syndrome that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 6. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for Sjogren’s syndrome. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with Sjogren’s syndrome. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.).

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The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to Sjogren’s syndrome: Pilocarpine •

Systemic - U.S. Brands: Salagen http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202726.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to Sjogren’s syndrome by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “Sjogren’s syndrome” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact

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information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for Sjogren’s syndrome: •

Cyclosporine Ophthalmic (trade name: Optimmune) http://www.rarediseases.org/nord/search/nodd_full?code=373

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Pilocarpine HC1 (trade name: Salagen) http://www.rarediseases.org/nord/search/nodd_full?code=379

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Treatment of mild to moderate keratoconjunctivitis http://www.rarediseases.org/nord/search/nodd_full?code=679

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Bromhexine http://www.rarediseases.org/nord/search/nodd_full?code=879

If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute9: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

9

These publications are typically written by one or more of the various NIH Institutes.

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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.10 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:11 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

10

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 11 See http://www.nlm.nih.gov/databases/databases.html.

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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway12 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.13 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Sjogren’s syndrome” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 8065 29 85 7 13 8199

HSTAT14 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.15 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.16 Simply search by “Sjogren’s syndrome” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

12

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

13

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 14 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 15 16

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists17 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.18 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.19 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

17 Adapted 18

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 19 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on Sjogren’s syndrome can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internetbased services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to Sjogren’s syndrome. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to Sjogren’s syndrome. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “Sjogren’s syndrome”:

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Adrenal Gland Disorders http://www.nlm.nih.gov/medlineplus/adrenalglanddisorders.html Autoimmune Diseases http://www.nlm.nih.gov/medlineplus/autoimmunediseases.html Congenital Heart Disease http://www.nlm.nih.gov/medlineplus/congenitalheartdisease.html Eye Diseases http://www.nlm.nih.gov/medlineplus/eyediseases.html Laboratory Tests http://www.nlm.nih.gov/medlineplus/laboratorytests.html Rheumatoid Arthritis http://www.nlm.nih.gov/medlineplus/rheumatoidarthritis.html Salivary Gland Disorders http://www.nlm.nih.gov/medlineplus/salivaryglanddisorders.html Scleroderma http://www.nlm.nih.gov/medlineplus/scleroderma.html Sickle Cell Anemia http://www.nlm.nih.gov/medlineplus/sicklecellanemia.html Sjogren's Syndrome http://www.nlm.nih.gov/medlineplus/sjogrenssyndrome.html

Within the health topic page dedicated to Sjogren’s syndrome, the following was listed: •

General/Overviews Sjogren's Syndrome Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00147

•

Diagnosis/Symptoms About Sjogren's Syndrome: Diagnosis Source: Sjogren's Syndrome Foundation http://www.sjogrens.org/syndrome/diagnosis.html Antinuclear Antibody Test Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/ana/test.html Rheumatoid Factor Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/rheumatoid/test.html

•

Specific Conditions/Aspects Dry Eye Source: American Academy of Ophthalmology http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZXQXXV1ED &sub_cat=118

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Dry Mouth Source: National Institute of Dental and Craniofacial Research http://www.nohic.nidcr.nih.gov/pubs/drymouth/dmouth.htm Sjogren's Syndrome and Lupus Source: Lupus Foundation of America http://www.lupus.org/education/brochures/sjogren.html •

From the National Institutes of Health Questions and Answers about Sjögren's Syndrome Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/hi/topics/sjogrens/index.htm Sjogren's Syndrome Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/sjogrens_doc.htm

•

Organizations National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/ National Institute of Dental and Craniofacial Research http://www.nidcr.nih.gov/ National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/ Sjogren's Syndrome Foundation http://www.sjogrens.org/

•

Research New Treatment May Prove to Be a Watershed for Those Suffering from Dry Eye Source: American College of Rheumatology http://www.rheumatology.org/press/am2003/pr13.asp

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on Sjogren’s syndrome. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search

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options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Sjogren Syndrome Source: Danbury, CT: National Organization for Rare Disorders, Inc. (NORD). 2002. 7 p. Contact: Available from National Organization for Rare Disorders, Inc. (NORD). 55 Kenosia Avenue, P.O. Box 1968, Danbury, CT 06813-1968. (203) 744-0100 or (800) 9996673. Fax (203) 798-2291. E-mail: [email protected]. Website: www.rarediseases.org. PRICE: Disease reports may be downloaded from the website for a fee of $7.50; contact NORD for price of print copies. Stock Number 6. Summary: This fact sheet on Sjogren syndrome is a printout from the National Organization for Rare Disorders (NORD) database. Sjogren's syndrome is characterized by a degeneration of the mucous-secreting glands, particularly the tear and saliva glands. The fact sheet presents a list of synonyms, a general discussion, and a brief discussion of the symptoms, causes, affected population, related disorders, and standard and investigational therapies for the syndrome. The fact sheet concludes with a brief list of resource organizations through which readers can obtain more information. 6 references. Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Questions and Answers about Sjogren's Syndrome Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6760

•

Sjogren's Syndrome Information Page Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2248 The NIH Search Utility

The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to Sjogren’s syndrome. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.

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Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Associations and Sjogren’s Syndrome The following is a list of associations that provide information on and resources relating to Sjogren’s syndrome: •

British Sjogren's Syndrome Association Telephone: (121) 455-6532 Fax: (121) 455-6532 Email: [email protected] Web Site: http://ourworld.compuserve.com/homepages.BSSAssociation Background: The British Sjogren's Syndrome Association (BSSA) is a registered charity dedicated to providing mutual support and information to individuals affected by Sjogren syndrome. Sjogren syndrome is an autoimmune disorder characterized by degeneration of the mucus-secreting glands, particularly the tear ducts of the eyes (lacrimal) and saliva glands of the mouth. Autoimmune disorders are caused when the body's natural defenses (antibodies, lymphocytes, etc.) against invading organisms suddenly begin to attack healthy tissue. Sjogren syndrome is also associated with inflammatory disorders such as arthritis or lupus. Founded in 1986, the BSSA strives to fulfill its mission to disseminate current information on the treatment of Sjogren syndrome to affected individuals and medical professionals. In addition to holding regular meetings in several locations throughout England, BSSA publishes journals, informational brochures, and a quarterly newsletter. Relevant area(s) of interest: Dacryosialoadenopathia Atrophicans, Keratoconjunctivitis Sicca, Sicca Syndrome

•

National Sjogren's Syndrome Association Telephone: (216) 292-3866 Toll-free: (800) 395-6772 Fax: (216) 292-4955 Email: [email protected]

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Web Site: www.sjogrenssyndrome.org Background: The National Sjogren's Syndrome Association (NSSA) is an international, non-profit organization whose main function is to provide emotional support to patients and their families, and educational information to both patients and health care professionals world-wide. The organization also sponsors support groups throughout the United States as well as national and regional conferences. NSSA supports scientific research which seeks to identify the cause of and find a cure for Sjogren's Syndrome. Relevant area(s) of interest: Keratoconjunctivitis Sicca, Sicca Syndrome •

Sjogren's Syndrome Foundation, Inc Telephone: (301) 718-0300 Toll-free: (800) 475-6473 Fax: (301) 718-0322 Web Site: http://www.sjogrens.org Background: The Sjogren s Syndrome Foundation is an international not-for-profit organization founded in 1983 to serve the needs of people affected by Sjogren s Syndrome. Sjogren's Syndrome, a disorder of unknown cause, is characterized by deficient moisture production of the mucous-secreting glands, particularly the tear ducts of the eyes (lacrimal) and the salivary glands of the mouth. Sjogren's Syndrome, which primarily affects middle-aged women, is thought to be due to an abnormal autoimmune response. The mission of the Foundation is to support and educate individuals affected by Sjogren s Syndrome and their families; educate health care professionals and the general public about the disorder; and stimulate interest in research toward improved treatments and an eventual cure. In addition, the Sjogren s Syndrome Foundation provides referrals to physicians who treat people with Sjogren s Syndrome; to local chapters; and to support groups. The Foundation offers postgraduate and student fellowships, and conducts conducts comprehensive symposia on Sjogren s Syndrome. Regional chapters and support groups conduct smaller regional and local gatherings. The Sjogren s Syndrome Foundation produces an extensive array of educational and support materials. These include audio and visual tape materials, a library of medical articles, a medical referral listing, a monthly newsletter, and a handbook entitled 'The Sjogren s Syndrome Handbook: An Authoritative Guide.'. Relevant area(s) of interest: Keratoconjunctivitis Sicca, Sicca Syndrome

•

Swedish Sjogren's Syndrome Association Telephone: +46 40 97 79 55 Fax: +46 46 30 73 53 Email: [email protected] Web Site: http://www.sjogrensyndrom.se Background: The Swedish Sjogren's Syndrome Association is an international not-forprofit organization dedicated to providing information and support to individuals with Sjogren's Syndrome, family members, and health care professionals. Sjogren's Syndrome, a disorder of unknown cause, is characterized by deficient moisture production of the mucous-secreting glands, particularly the tear ducts of the eyes (lacrimal) and the salivary glands of the mouth. Associated symptoms and physical abnormalities may include abnomal dryness, itching, and burning of the eyes (keratoconjunctivitis sicca); abnormal dryness of the mouth, resulting in cavities, other dental disorders, and loss of odor and taste sensations; and, when the lungs are affected,

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increased susceptibility to repeated respiratory infections. Many affected individuals also experience rheumatoid arthritis. Sjogren's Syndrome, which primarily affects middle-aged women, is thought to be due to an abnormal autoimmune response. Established in 1989, the Swedish Sjogren's Syndrome Association provides networking opportunities that enable affected individuals and family members to exchange information, support, and resources; engages in patient education; and offers a variety of materials including reports and a regular newsletter. The Association also has a web site on the Internet in both English and Swedish that explains the history of Sjogren's Syndrome, discusses current research in Sweden and around the world, provides information concerning the disorder, and offers dynamic linkage to other helpful sources of information on the Internet. Relevant area(s) of interest: Keratoconjunctivitis Sicca, Sicca Syndrome

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to Sjogren’s syndrome. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with Sjogren’s syndrome. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about Sjogren’s syndrome. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “Sjogren’s syndrome” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information.

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The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “Sjogren’s syndrome”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “Sjogren’s syndrome” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “Sjogren’s syndrome” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.20

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

20

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)21: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

21

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on Sjogren’s syndrome: •

Basic Guidelines for Sjogren’s Syndrome Keratoconjunctivitis sicca Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000426.htm

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Signs & Symptoms for Sjogren’s Syndrome Tearing, decreased Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003087.htm

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Diagnostics and Tests for Sjogren’s Syndrome Visual acuity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003396.htm

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Nutrition for Sjogren’s Syndrome Vitamin a deficiency Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002400.htm

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Background Topics for Sjogren’s Syndrome Conjunctiva Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002326.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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SJOGREN’S SYNDROME DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Actin: Essential component of the cell skeleton. [NIH] Acuity: Clarity or clearness, especially of the vision. [EU] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenaline: A hormone. Also called epinephrine. [NIH]

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Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU]

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Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amylase: An enzyme that helps the body digest starches. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anchorage: In dentistry, points of retention of fillings and artificial restorations and appliances. [NIH]

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Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Anhydrous: Deprived or destitute of water. [EU] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidepressant: A drug used to treat depression. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH]

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Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aquaporins: Membrane proteins which facilitate the passage of water. They are members of the family of membrane channel proteins which includes the lens major intrinsic protein and bacterial glycerol transporters. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Arthropathy: Any joint disease. [EU] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH]

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Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmune Hepatitis: A liver disease caused when the body's immune system destroys liver cells for no known reason. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Beta 2-Microglobulin: An 11 kDa protein associated with the outer membrane of many cells including lymphocytes. It is the small subunit of the MHC class I molecule. Association with

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beta 2-microglobulin is generally required for the transport of class I heavy chains from the endoplasmic reticulum to the cell surface. Beta 2-microglobulin is present in small amounts in serum, csf, and urine of normal people, and to a much greater degree in the urine and plasma of patients with tubular proteinemia, renal failure, or kidney transplants. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biofilms: Films of bacteria or other microbial organisms, usually embedded in extracellular polymers such as implanted medical devices, which adhere to surfaces submerged in, or subjected to, aquatic environments (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). Biofilms consist of multilayers of microbial cells glued together to form microbial communities which are highly resistant to both phagocytes and antibiotics. [NIH] Biogenesis: The origin of life. It includes studies of the potential basis for life in organic compounds but excludes studies of the development of altered forms of life through mutation and natural selection, which is evolution. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived

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constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotinylation: Incorporation of biotinyl groups into molecules. [NIH] Bladder: The organ that stores urine. [NIH] Blepharitis: Inflammation of the eyelids. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Morphogenetic Proteins: Bone-growth regulatory factors that are members of the transforming growth factor-beta superfamily of proteins. They are synthesized as large precursor molecules which are cleaved by proteolytic enzymes. The active form can consist of a dimer of two identical proteins or a heterodimer of two related bone morphogenetic proteins. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures.

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[NIH]

Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]

Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsular: Cataract which is initiated by an opacification at the surface of the lens. [NIH] Carbachol: A slowly hydrolyzed cholinergic agonist that acts at both muscarinic and nicotinic receptors. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH]

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Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that

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develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Cheilitis: Inflammation of the lips. It is of various etiologies and degrees of pathology. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotherapeutics: Noun plural but singular or plural in constructions : chemotherapy. [EU]

Chemotherapy: Treatment with anticancer drugs. [NIH] Chenodeoxycholic Acid: A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chlorhexidine: Disinfectant and topical anti-infective agent used also as mouthwash to prevent oral plaque. [NIH] Cholangitis: Inflammation of a bile duct. [NIH] Choleretic: A choleretic agent. [EU] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clathrin: The main structural coat protein of coated vesicles which play a key role in the

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intracellular transport between membranous organelles. Clathrin also interacts with cytoskeletal proteins. [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles are covered with a lattice-like network of coat proteins, such as clathrin, coat protein complex proteins, or caveolins. [NIH] Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colostrum: The thin, yellow, serous fluid secreted by the mammary glands during pregnancy and immediately postpartum before lactation begins. It consists of immunologically active substances, white blood cells, water, protein, fat, and carbohydrates. [NIH]

Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with

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lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Connective Tissue Diseases: A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides. [NIH]

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Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contrast medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Crowns: A prosthetic restoration that reproduces the entire surface anatomy of the visible natural crown of a tooth. It may be partial (covering three or more surfaces of a tooth) or complete (covering all surfaces). It is made of gold or other metal, porcelain, or resin. [NIH] CSF: Cerebrospinal fluid. The fluid flowing around the brain and spinal cord. CSF is produced in the ventricles of the brain. [NIH] Curative: Tending to overcome disease and promote recovery. [EU]

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Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cystitis: Inflammation of the urinary bladder. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deglutition: The process or the act of swallowing. [NIH] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Abutments: Natural teeth or teeth roots used as anchorage for a fixed or removable denture or other prosthesis (such as an implant) serving the same purpose. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Dentists: Individuals licensed to practice dentistry. [NIH] Dentition: The teeth in the dental arch; ordinarily used to designate the natural teeth in position in their alveoli. [EU] Dentures: An appliance used as an artificial or prosthetic replacement for missing teeth and adjacent tissues. It does not include crowns, dental abutments, nor artificial teeth. [NIH]

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Depigmentation: Removal or loss of pigment, especially melanin. [EU] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Desiccation: Removal of moisture from a substance (chemical, food, tissue, etc.). [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disinfection: Rendering pathogens harmless through the use of heat, antiseptics, antibacterial agents, etc. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH]

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Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Dry Eye Syndrome: A common condition that occurs when the eyes do not produce enough tears to keep the eye moist and comfortable. Common symptoms of dry eye include pain, stinging, burning, scratchiness, and intermittent blurring of vision. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dynein: A transport protein that normally binds proteins to the microtubule. [NIH] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysphagia: Difficulty in swallowing. [EU] Echinacea: A genus of perennial herbs used topically and internally. It contains echinacoside, glycosides, inulin, isobutyl amides, resin, and sesquiterpenes. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Effusion: The escape of fluid into a part or tissue, as an exudation or a transudation. [EU] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU]

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Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endogenous Retroviruses: Retroviruses that have integrated into the germline (Proviruses) that have lost infectious capability but retained the capability to transpose. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH]

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Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Episcleritis: Inflammation of the episclera and/or the outer layers of the sclera itself. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] ERV: The expiratory reserve volume is the largest volume of gas that can be expired from the end-expiratory level. [NIH] Erythrocyte Indices: Quantification of size and cell hemoglobin content or concentration of the erythrocyte, usually derived from erythrocyte count, blood hemoglobin concentration, and hematocrit. Includes the mean cell volume (MCV), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC). Use also for cell diameter and thickness. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estrogen: One of the two female sex hormones. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH]

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Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excrete: To get rid of waste from the body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] Expiratory Reserve Volume: The extra volume of air that can be expired with maximum effort beyond the level reached at the end of a normal, quiet expiration. Common abbreviation is ERV. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Eye socket: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Facial: Of or pertaining to the face. [EU] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Fallopian tube: The oviduct, a muscular tube about 10 cm long, lying in the upper border of the broad ligament. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue

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development. [NIH] Fetal Heart: The heart of the fetus of any viviparous animal. It refers to the heart in the postembryonic period and is differentiated from the embryonic heart (heart/embryology) only on the basis of time. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Follicles: Shafts through which hair grows. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

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Gastritis: Inflammation of the stomach. [EU] Gastroenterologist: A doctor who specializes in diagnosing and treating disorders of the digestive system. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germinal Center: The activated center of a lymphoid follicle in secondary lymphoid tissue where B-lymphocytes are stimulated by antigens and helper T cells (T-lymphocytes, helperinducer) are stimulated to generate memory cells. [NIH] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic

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(drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH]

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Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemophilia: Refers to a group of hereditary disorders in which affected individuals fail to make enough of certain proteins needed to form blood clots. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH]

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Hepatitis C: A form of hepatitis, similar to type B post-transfusion hepatitis, but caused by a virus which is serologically distinct from the agents of hepatitis A, B, and E, and which may persist in the blood of chronic asymptomatic carriers. Hepatitis C is parenterally transmitted and associated with transfusions and drug abuse. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterodimer: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Histology: The study of tissues and cells under a microscope. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]

Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydration: Combining with water. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive

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isotope tritium. [NIH] Hydrogen Bonding: A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds. [NIH]

Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypersplenism: Condition characterized by splenomegaly, some reduction in the number of circulating blood cells in the presence of a normal or hyperactive bone marrow, and the potential for reversal by splenectomy. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypophysis: A remnant of the entodermal pouch of Rathke beneath the mucous membrane of the pharynx, which shows pituitary tissue. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization

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involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Impaction: The trapping of an object in a body passage. Examples are stones in the bile duct or hardened stool in the colon. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Impotent: Unable to have an erection adequate for sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a

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specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important

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processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-10: Factor that is a coregulator of mast cell growth. It is produced by T-cells and B-cells and shows extensive homology with the Epstein-Barr virus BCRFI gene. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin

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or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Ion-Selective Electrodes: Electrodes which can be used to measure the concentration of particular ions in cells, tissues, or solutions. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isotonic: A biological term denoting a solution in which body cells can be bathed without a net flow of water across the semipermeable cell membrane. Also, denoting a solution having the same tonicity as some other solution with which it is compared, such as physiologic salt solution and the blood serum. [EU] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kallikrein-Kinin System: A system produced in the distal nephron of the kidney. Its components are kallikrein, kinins, kininase I and II, and enkephalinase. It is involved in mediation and modulation of the renin-angiotensin-aldosterone system, prostaglandins, vasopressins, and in the regulation of sodium-water balance, renal hemodynamics, and particularly blood pressure. The system participates in the control of renal functions and the physiopathology of renal diseases. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratoconjunctivitis: Simultaneous inflammation of the cornea and conjunctiva. [NIH] Keratoconjunctivitis Sicca: Drying and inflammation of the conjunctiva as a result of insufficient lacrimal secretion. When found in association with xerostomia and polyarthritis, it is called Sjogren's syndrome. [NIH] Keratolytic: An agent that promotes keratolysis. [EU]

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Kinesin: A microtubule-associated mechanical adenosine triphosphatase, that uses the energy of ATP hydrolysis to move organelles along microtubules toward the plus end of the microtubule. The protein is found in squid axoplasm, optic lobes, and in bovine brain. Bovine kinesin is a heterotetramer composed of two heavy (120 kDa) and two light (62 kDa) chains. EC 3.6.1.-. [NIH] Lacrimal: Pertaining to the tears. [EU] Lacrimal gland: The small almond-shaped structure that produces tears; located just above the outer corner of the eye. [NIH] Lactation: The period of the secretion of milk. [EU] Lactobacillus: A genus of gram-positive, microaerophilic, rod-shaped bacteria occurring widely in nature. Its species are also part of the many normal flora of the mouth, intestinal tract, and vagina of many mammals, including humans. Pathogenicity from this genus is rare. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laryngeal: Having to do with the larynx. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lethal: Deadly, fatal. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH]

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Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]

Lubricants: Oily or slippery substances. [NIH] Lubrication: The application of a substance to diminish friction between two surfaces. It may refer to oils, greases, and similar substances for the lubrication of medical equipment but it can be used for the application of substances to tissue to reduce friction, such as lotions for skin and vaginal lubricants. [NIH] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU]

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Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

MALT lymphoma: Mucosa-associated lymphoid tissue lymphoma. A type of cancer that arises in cells in mucosal tissue that are involved in antibody production. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meibomian: A series of simple, branched, alveolar, sebaceous glands, located in the tarso of the eyelids, whose ducts empty into the eyelid margins in line with and lateral to the lacrimal puncta. [NIH] Meibomian Glands: The sebaceous glands situated on the inner surface of the eyelids between the tarsal plates and conjunctiva. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into

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immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Methylcellulose: Methylester of cellulose. Methylcellulose is used as an emulsifying and suspending agent in cosmetics, pharmaceutics and the chemical industry. It is used therapeutically as a bulk laxative. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Mice Minute Virus: The type species of parvovirus prevalent in mouse colonies and found as a contaminant of many transplanted tumors or leukemias. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH]

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Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Miotic: 1. Pertaining to, characterized by, or producing miosis : contraction of the pupil. 2. An agent that causes the pupil to contract. 3. Meiotic: characterized by cell division. [EU] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate mitogen-activated protein kinases and are themselves phosphorylated by MAP kinase kinase kinases. JNK kinases (also known as SAPK kinases) are a subfamily. EC 2.7.10.- [NIH] Mitogen-Activated Protein Kinases: A superfamily of protein-serine-threonine kinases that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by mitogen-activated protein kinase kinases which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP kinase kinase kinases). Families of these mitogen-activated protein kinases (MAPKs) include extracellular signal-regulated kinases (ERKs), stress-activated protein kinases (SAPKs) (also known as c-jun terminal kinases (JNKs)), and p38-mitogen-activated protein kinases. EC 2,7,1.- [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells.

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Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]

Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mouth Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscarinic Agonists: Drugs that bind to and activate muscarinic cholinergic receptors (receptors, muscarinic). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelitis: Inflammation of the spinal cord. Relatively common etiologies include infections; autoimmune diseases; spinal cord; and ischemia (see also spinal cord vascular diseases). Clinical features generally include weakness, sensory loss, localized pain, incontinence, and other signs of autonomic dysfunction. [NIH] Myocardial Contraction: Contractile activity of the heart. [NIH]

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Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myositis: Inflammation of a voluntary muscle. [EU] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephron: A tiny part of the kidneys. Each kidney is made up of about 1 million nephrons, which are the working units of the kidneys, removing wastes and extra fluids from the blood. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuroeffector Junction: The synapse between a neuron (presynaptic) and an effector cell other than another neuron (postsynaptic). Neuroeffector junctions include synapses onto

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muscles and onto secretory cells. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nursing Care: Care given to patients by nursing service personnel. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division

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and the completion of the second maturation division. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteomalacia: A condition marked by softening of the bones (due to impaired mineralization, with excess accumulation of osteoid), with pain, tenderness, muscular weakness, anorexia, and loss of weight, resulting from deficiency of vitamin D and calcium. [EU]

Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar

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gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Parotitis: Inflammation of the parotid gland. [NIH] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Parturition: The act or process of given birth to a child. [EU] Parvovirus: A genus of the family Parvoviridae, subfamily Parvovirinae, infecting a variety of vertebrates including humans. Parvoviruses are responsible for a number of important diseases but also can be non-pathogenic in certain hosts. The type species is mice minute virus. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathology, Oral: A dental specialty concerned with pathology of the oral cavity. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Care Management: Generating, planning, organizing, and administering medical and nursing care and services for patients. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Penicillamine: 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perennial: Lasting through the year of for several years. [EU] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels.

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[NIH]

Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]

Periorbital: Situated around the orbit, or eye socket. [EU] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [NIH] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [NIH] Phorbol Esters: Tumor-promoting compounds obtained from croton oil (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylates: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the

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formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pilocarpine: A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmids: Any extrachromosomal hereditary determinant. Plasmids are self-replicating circular molecules of DNA that are found in a variety of bacterial, archaeal, fungal, algal, and plant species. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic

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weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pneumonia: Inflammation of the lungs. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyarthritis: An inflammation of several joints together. [EU] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Precipitation: The act or process of precipitating. [EU] Precipitins: Antibodies which elicit precipitation when combined with antigen. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU]

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Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Preoperative: Preceding an operation. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to

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indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Kinase C: An enzyme that phosphorylates proteins on serine or threonine residues in the presence of physiological concentrations of calcium and membrane phospholipids. The additional presence of diacylglycerols markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. EC 2.7.1.-. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Protein Subunits: Single chains of amino acids that are the units of a multimeric protein. They can be identical or non-identical subunits. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors. EC 2.7.10. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other

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aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Pseudohypoaldosteronism: A hereditary disorder characterized by salt wasting and growth retardation, presenting in infancy as high levels of urinary sodium despite hyponatremia, hyperkalemia, hyperreninemia, and elevated aldosterone levels. The mode of inheritance is probably autosomal dominant, affecting electrolyte secretion in the kidney tubule. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Ptyalism: Irritation of the mouth with increased saliva formation seen in mercury intoxication. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quiescent: Marked by a state of inactivity or repose. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH]

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Radioactive: Giving off radiation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Ranula: A form of retention cyst of the floor of the mouth, usually due to obstruction of the ducts of the submaxillary or sublingual glands, presenting a slowly enlarging painless deep burrowing mucocele of one side of the mouth. It is also called sublingual cyst and sublingual ptyalocele. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Muscarinic: One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for muscarine over nicotine. There are several subtypes (usually M1, M2, M3.) that are characterized by their cellular actions, pharmacology, and molecular biology. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is

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incompetent. [EU] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Renal tubular acidosis: A rare disorder in which structures in the kidney that filter the blood are impaired, producing using that is more acid than normal. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested

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as possible causes. [NIH] Rheumatology: A subspecialty of internal medicine concerned with the study of inflammatory or degenerative processes and metabolic derangement of connective tissue structures which pertain to a variety of musculoskeletal disorders, such as arthritis. [NIH] Ribonuclease: RNA-digesting enzyme. [NIH] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [NIH] Ribonucleoproteins: Proteins conjugated with ribonucleic acids (RNA) or specific RNA. Many viruses are ribonucleoproteins. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rituximab: A type of monoclonal antibody used in cancer detection or therapy. Monoclonal antibodies are laboratory-produced substances that can locate and bind to cancer cells. [NIH] Rod: A reception for vision, located in the retina. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary Gland Neoplasms: Tumors or cancer of the salivary glands. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salivation: 1. The secretion of saliva. 2. Ptyalism (= excessive flow of saliva). [EU] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Scalpel: A small pointed knife with a convex edge. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Scleritis: Refers to any inflammation of the sclera including episcleritis, a benign condition affecting only the episclera, which is generally short-lived and easily treated. Classic

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scleritis, on the other hand, affects deeper tissue and is characterized by higher rates of visual acuity loss and even mortality, particularly in necrotizing form. Its characteristic symptom is severe and general head pain. Scleritis has also been associated with systemic collagen disease. Etiology is unknown but is thought to involve a local immune response. Treatment is difficult and includes administration of anti-inflammatory and immunosuppressive agents such as corticosteroids. Inflammation of the sclera may also be secondary to inflammation of adjacent tissues, such as the conjunctiva. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Secretin: A hormone made in the duodenum. Causes the stomach to make pepsin, the liver to make bile, and the pancreas to make a digestive juice. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensory loss: A disease of the nerves whereby the myelin or insulating sheath of myelin on the nerves does not stay intact and the messages from the brain to the muscles through the nerves are not carried properly. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH]

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Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sharpness: The apparent blurring of the border between two adjacent areas of a radiograph having different optical densities. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Sialography: Radiography of the salivary glands or ducts following injection of contrast medium. [NIH] Sialorrhea: Increased salivary flow. [NIH] Sicca: Failure of lacrimal secretion, keratoconjunctivitis sicca, failure of secretion of the salivary glands and mucous glands of the upper respiratory tract and polyarthritis. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH]

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Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Somatic mutations: Alterations in DNA that occur after conception. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. These alterations can (but do not always) cause cancer or other diseases. [NIH] Somnolence: Sleepiness; also unnatural drowsiness. [EU] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Vascular Diseases: Hypoxic-ischemic and hemorrhagic disorders of the spinal cord. Arteriosclerosis, emboli, and vascular malformations are potential causes of these conditions. [NIH]

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Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenectomy: An operation to remove the spleen. [NIH] Splenomegaly: Enlargement of the spleen. [NIH] Squamous: Scaly, or platelike. [EU] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Sublingual: Located beneath the tongue. [EU]

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Submandibular: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Synovial: Of pertaining to, or secreting synovia. [EU] Synovial Membrane: The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes synovial fluid. [NIH] Synovitis: Inflammation of a synovial membrane. It is usually painful, particularly on motion, and is characterized by a fluctuating swelling due to effusion within a synovial sac. Synovitis is qualified as fibrinous, gonorrhoeal, hyperplastic, lipomatous, metritic, puerperal, rheumatic, scarlatinal, syphilitic, tuberculous, urethral, etc. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems.

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Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Tear Gases: Gases that irritate the eyes, throat, or skin. Severe lacrimation develops upon irritation of the eyes. [NIH] Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] Telophase: The final phase of cell division, in which two daughter nuclei are formed, the cytoplasm divides, and the chromosomes lose their distinctness and are transformed into chromatin networks. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrush: A disease due to infection with species of fungi of the genus Candida. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroiditis: Inflammation of the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH]

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Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonicity: The normal state of muscular tension. [NIH] Tooth Loss: The failure to retain teeth as a result of disease or injury. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH]

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Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [NIH]

Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]

Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tubal ligation: An operation to tie the fallopian tubes closed. This procedure prevents pregnancy by blocking the passage of eggs from the ovaries to the uterus. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH]

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Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]

Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Ursodeoxycholic Acid: An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway.

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[NIH]

Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasopressins: Octapeptide antidiuretic hormones released by the neurohypophysis of all vertebrates (chemical composition varies with species). They control water metabolism and balance by regulating lung, gill, kidney, etc., and water loss, and also contract smooth muscle. They may also be neurotransmitters. Also included are synthetic vasopressin derivatives. Vasopressins are used pharmacologically as renal agents, vasoconstrictor agents, and hemostatics. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villous: Of a surface, covered with villi. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Proteins: Proteins found in any species of virus. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [NIH] Vitamin D: The vitamin that mediates intestinal calcium absorption, bone calcium metabolism, and probably muscle activity. It usually acts as a hormone precursor, requiring 2 stages of metabolism before reaching actual hormonal form. It is isolated from fish liver oils and used in the treatment and prevention of rickets. [NIH] Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH]

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Watermelon Stomach: Parallel red sores in the stomach that look like the stripes on a watermelon. Frequently seen with cirrhosis. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] Xerophthalmia: Dryness of the eye surfaces caused by deficiency of tears or conjunctival secretions. It may be associated with vitamin A deficiency, trauma, or any condition in which the eyelids do not close completely. [NIH] Xerostomia: Decreased salivary flow. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

199

INDEX A Abdomen, 139, 146, 157, 167, 170, 191 Abdominal, 139, 177, 178 Aberrant, 20, 29, 31, 139 Acceptor, 139, 170, 177 Acetylcholine, 4, 7, 16, 30, 68, 69, 139, 149, 176 Acidity, 139, 179 Acidosis, 86, 139 Actin, 139, 174, 175 Acuity, 10, 137, 139 Adaptability, 139, 148 Adaptation, 139, 180 Adenocarcinoma, 102, 139 Adenosine, 139, 169, 179 Adenovirus, 17, 139 Adrenal Cortex, 139, 140, 152, 182 Adrenal Glands, 139, 141 Adrenaline, 30, 139 Adrenergic, 17, 140, 154, 157 Adrenergic Agonists, 17, 140 Adverse Effect, 34, 140, 189 Affinity, 7, 34, 140, 190 Agar, 140, 180 Agonist, 5, 77, 85, 140, 147, 154, 180 Airway, 6, 47, 106, 140 Albumin, 4, 88, 140, 180 Aldosterone, 140, 168, 184 Algorithms, 140, 146 Alkaline, 139, 140, 141, 147, 179 Alkaloid, 4, 140 Alleles, 26, 140 Allergen, 22, 140 Alopecia, 141, 153 Alpha Particles, 141, 184 Alternative medicine, 107, 141 Alveoli, 141, 153 Amino acid, 9 Amino Acid Sequence, 9, 141, 142, 160 Amino-terminal, 59, 141 Ammonia, 141, 192, 196 Amylase, 4, 141 Amyloid, 141 Amyloidosis, 65, 66, 141 Anaesthesia, 141, 166 Analog, 13, 141 Analytes, 124, 141 Anaplasia, 141

Anatomical, 141, 149, 156, 165, 188 Anchorage, 20, 141, 153 Androgens, 8, 15, 27, 139, 142, 152 Anemia, 26, 124, 142, 162 Anesthesia, 140, 142 Angiogenesis, 142, 171 Anhydrous, 82, 142 Animal model, 7, 9, 34, 142 Anions, 140, 142, 168 Anorexia, 142, 177, 196 Antibacterial, 91, 142, 154, 190 Antibiotic, 142, 178, 190 Antibodies, 5, 7, 9, 16, 18, 22, 23, 93, 97, 127 Antibody, 9, 16, 23, 82, 124 Anticoagulant, 142, 183 Antidepressant, 142, 159 Antigen, 9, 23, 32, 35, 61, 140, 142, 151, 160, 163, 164, 165, 166, 171, 181 Anti-infective, 142, 149, 164 Anti-inflammatory, 8, 14, 34, 142, 152, 160, 165, 188 Anti-Inflammatory Agents, 143, 152 Antimetabolite, 143, 172 Antimicrobial, 88, 143 Antineoplastic, 143, 152, 153, 172 Apoptosis, 4, 15, 17, 23, 26, 30, 38, 51, 53, 56, 64, 71, 143, 148 Aquaporins, 7, 29, 38, 143 Aqueous, 10, 17, 21, 32, 143, 144, 153, 155, 164, 169 Arachidonic Acid, 143, 182 Arterial, 143, 164, 183 Arteries, 143, 146, 152, 172 Arterioles, 143, 146, 147 Artery, 143, 152, 178, 184 Arthropathy, 63, 143 Assay, 16, 22, 39, 143, 165 Asymptomatic, 16, 33, 143, 163, 178 Ataxia, 74, 143, 193 Atopic, 47, 143 Atrophy, 27, 143 Autacoids, 143, 165 Autoantibodies, 3, 7, 16, 23, 31, 33, 36, 106, 108 Autoantigens, 7, 8, 17, 18, 27, 28, 34, 68, 143, 144 Autodigestion, 144, 178

200

Sjogren's syndrome

Autoimmune Hepatitis, 82, 144 Autoimmunity, 8, 9, 23, 32, 37, 47, 60, 65, 79, 144 Autonomic, 39, 42, 44, 74, 139, 144, 174, 176, 179 B Bacteria, 142, 144, 145, 153, 156, 158, 161, 169, 172, 189, 190, 194, 196 Bactericidal, 22, 144 Bacteriophage, 144, 180, 194 Bacterium, 108, 144 Bacteriuria, 144, 196 Barbiturate, 144, 193 Basal Ganglia, 143, 144 Basal Ganglia Diseases, 143, 144 Base, 144, 153, 160, 168, 179, 196 Basophils, 144, 161, 169 Benign, 63, 102, 103, 144, 162, 175, 185, 187, 197 Beta 2-Microglobulin, 88, 144 Bile, 33, 145, 149, 159, 165, 168, 170, 182, 188, 191, 196 Bile Acids, 145, 191 Bile Acids and Salts, 145 Bile duct, 33, 145, 149, 159, 165, 182 Bile Pigments, 145, 168 Biliary, 28, 33, 70, 83, 108, 145, 178 Biliary Tract, 145, 178 Bilirubin, 140, 145, 159, 164 Binding Sites, 22, 145 Bioavailable, 8, 145 Biochemical, 12, 17, 19, 21, 30, 41, 59, 140, 143, 145, 188 Biofilms, 15, 145 Biogenesis, 25, 33, 145 Biological response modifier, 145, 167 Biological therapy, 145, 162 Biopsy, 37, 41, 42, 58, 73, 78, 91, 92, 94, 103, 145 Biopsy specimen, 42, 73, 145 Biotechnology, 16, 35, 36, 107, 119, 145 Biotinylation, 25, 146 Bladder, 146, 153, 165, 174, 196 Blepharitis, 14, 146 Bloating, 97, 146, 165 Blood Cell Count, 96, 146, 162 Blood Coagulation, 146, 147, 193 Blood Platelets, 146, 188, 193 Blood pressure, 49, 146, 164, 168, 173, 190 Blood vessel, 142, 146, 147, 149, 156, 160, 168, 170, 172, 189, 190, 191, 193, 197 Blot, 17, 28, 146

Body Fluids, 146, 155, 190 Bone Density, 94, 146 Bone Marrow, 146, 160, 161, 164, 165, 170, 174, 191 Bone Morphogenetic Proteins, 21, 146 Bowel, 62, 146, 154, 167, 169, 191 Bowel Movement, 146, 154, 191 Brachytherapy, 146, 167, 168, 184, 198 Branch, 135, 146, 155, 170, 178, 184, 190, 193 Breeding, 32, 147 Buccal, 94, 147, 170 C Calcium, 74, 147, 149, 150, 171, 177, 183, 189, 197 Candidiasis, 5, 31, 54, 147 Candidosis, 147 Capillary, 29, 147, 197 Capsular, 33, 147 Carbachol, 8, 19, 147 Carbohydrate, 147, 152, 161, 181 Carcinogenic, 147, 166, 176, 182, 191 Carcinoma, 102, 147 Cardiac, 30, 37, 147, 156, 157, 175, 191 Cardiovascular, 30, 42, 85, 147, 188 Cardiovascular System, 85, 147 Case report, 70, 76, 83, 108, 147 Case series, 50, 147 Caspase, 31, 76, 148 Cataract, 7, 147, 148 Cations, 148, 168 Celiac Disease, 108, 148 Cell, 4, 6, 7, 8, 9, 10, 13, 14, 20, 22, 24, 25, 27, 29, 30, 32, 33, 34, 35, 82, 83, 85, 89, 93, 102, 124 Cell Adhesion, 79, 148, 166 Cell Count, 96, 148 Cell Death, 15, 27, 52, 61, 68, 143, 148, 160 Cell Differentiation, 20, 22, 35, 148, 189 Cell Division, 144, 148, 162, 167, 173, 180, 182, 188, 193 Cell membrane, 7, 85, 148, 154, 168, 179 Cell proliferation, 27, 148, 189 Cell Survival, 148, 162 Cell Transplantation, 148 Cellulose, 148, 159, 172, 180 Central Nervous System, 88, 139, 148, 155, 159, 161, 162, 174, 177, 188 Central Nervous System Infections, 148, 162 Cerebellar, 143, 148, 185 Cerebral, 46, 82, 143, 144, 148, 149, 157

201

Cerebral Cortex, 143, 148, 157 Cerebrum, 148, 149 Character, 149, 153, 161 Cheilitis, 50, 102, 149 Chemokines, 18, 34, 62, 149 Chemotherapeutics, 26, 149 Chemotherapy, 30, 149 Chenodeoxycholic Acid, 149, 196 Chin, 84, 149, 172 Chlorhexidine, 49, 84, 149 Cholangitis, 33, 149 Choleretic, 149, 196 Cholesterol, 145, 149, 159, 191 Cholinergic, 5, 6, 8, 17, 83, 147, 149, 174, 185 Chromatin, 143, 149, 193 Chromosomal, 25, 149, 186 Chromosome, 80, 149, 169, 188 Chronic, 6, 8, 11, 15, 26, 27, 33, 94, 97, 101, 108, 109 Chronic Disease, 26, 149, 150 Cirrhosis, 28, 33, 70, 83, 108, 149, 182, 198 Citric Acid, 92, 149 Citrus, 149 Clathrin, 30, 149, 150 Clinical trial, 6, 13, 33, 83, 91, 98, 119, 150, 152, 154, 183, 185 Clone, 9, 29, 42, 150 Cloning, 146, 150 Coated Vesicles, 149, 150 Cod Liver Oil, 150, 155 Cofactor, 150, 183, 193 Collagen, 74, 141, 150, 151, 158, 159, 171, 182, 188 Collagen disease, 150, 188 Colloidal, 140, 150, 179 Colon, 150, 165, 169 Colostrum, 69, 150 Complement, 82, 150, 166, 171, 180 Complete remission, 65, 151, 186 Computational Biology, 119, 151 Computed tomography, 46, 103, 146, 151 Computerized tomography, 151 Conception, 151, 159, 190, 191 Concomitant, 16, 151 Conduction, 96, 151 Congestive heart failure, 30, 151 Conjugated, 145, 149, 151, 187 Conjunctiva, 14, 97, 138, 151, 168, 171, 188 Conjunctivitis, 14, 22, 151 Connective Tissue, 11, 16, 55, 95, 146, 150, 151, 159, 170, 172, 186, 187, 192

Connective Tissue Cells, 151 Connective Tissue Diseases, 16, 55, 151 Contraindications, ii, 152 Contrast medium, 152, 189 Control group, 6, 152 Controlled study, 69, 70, 152 Coordination, 152, 174 Cornea, 10, 21, 85, 152, 168, 187, 191, 196 Coronary, 152, 172 Coronary Thrombosis, 152, 172 Corpus, 152, 170, 182, 197 Corpus Luteum, 152, 170, 182 Corticosteroid, 88, 152, 182 Cortisol, 140, 152 Cranial, 152, 158, 162, 177, 179 Craniocerebral Trauma, 144, 152, 162, 193, 194 Crowns, 152, 153 CSF, 52, 145, 152 Curative, 152, 187, 193 Cutaneous, 23, 56, 71, 83, 147, 153, 168, 170 Cyclic, 153, 183 Cyclophosphamide, 65, 153 Cyst, 102, 153, 185 Cystitis, 62, 153 Cytokine, 13, 26, 87, 153, 193 Cytoplasm, 143, 144, 148, 153, 156, 161, 174, 187, 193 Cytoskeleton, 153, 166, 173 Cytotoxic, 6, 61, 68, 153, 165, 185, 189 Cytotoxicity, 7, 153 D Defense Mechanisms, 153, 167 Degenerative, 153, 162, 187 Deglutition, 19, 153 Dehydroepiandrosterone, 65, 66, 94, 153 Deletion, 9, 143, 153 Density, 94, 146, 153, 177, 190 Dental Abutments, 153 Dental Caries, 5, 153 Dentists, 101, 153 Dentition, 15, 153 Dentures, 15, 153 Depigmentation, 154, 197 Depolarization, 154, 189 Desiccation, 4, 10, 154 Diabetes Mellitus, 154, 161, 162 Diagnostic procedure, 107, 154 Diarrhea, 108, 154 Digestion, 145, 146, 154, 155, 165, 167, 170, 191, 196

202

Sjogren's syndrome

Digestive system, 98, 154, 160, 174 Dilatation, 154, 182 Dimerization, 24, 154 Direct, iii, 29, 111, 154, 185, 192 Disinfection, 15, 154 Dissociation, 140, 154 Distal, 154, 168, 179, 182 Dizziness, 97, 154, 197 Dopamine, 154, 176, 179 Double-blind, 49, 84, 154 Drug Interactions, 112, 154 Drug Tolerance, 155, 194 Dry Eye Syndrome, 10, 22, 93, 97, 155 Duct, 6, 20, 27, 33, 102, 155, 158, 187, 192 Duodenum, 145, 155, 188, 191 Dynein, 18, 155 Dyspepsia, 108, 155, 165 Dysphagia, 72, 155 E Echinacea, 45, 155 Ectopic, 43, 48, 51, 155 Effector, 18, 43, 139, 150, 155, 175 Efferent, 9, 155, 158 Efficacy, 54, 88, 96, 155 Effusion, 155, 192 Elastic, 155, 161, 190 Elastin, 150, 151, 155, 158 Electrocardiogram, 96, 155 Electrolyte, 12, 20, 140, 152, 155, 173, 184, 190, 196 Electrophysiological, 7, 155 Embryo, 148, 155, 166 Embryology, 155, 159 Emulsion, 97, 155 Enamel, 153, 156 Endocarditis, 147, 156 Endocrine System, 156 Endocrinology, 27, 156 Endocytosis, 30, 156 Endogenous, 8, 28, 144, 154, 156 Endogenous Retroviruses, 28, 156 Endorphins, 156, 176 Endothelial cell, 48, 156, 193 Endothelium, 29, 156 Endothelium, Lymphatic, 156 Endothelium, Vascular, 156 Endotoxin, 156, 195 Enkephalins, 156, 176 Environmental Health, 118, 120, 156 Enzymatic, 141, 147, 151, 153, 156, 186 Enzyme, 10, 25, 33 Eosinophil, 84, 156

Eosinophilic, 156, 157 Epidermal, 8, 17, 157, 197 Epidermal Growth Factor, 8, 17, 157 Epidermis, 157, 184 Epigastric, 157, 177 Epinephrine, 139, 140, 154, 157, 176, 195 Episcleritis, 14, 157, 187 Epithelial, 4, 6, 12, 15, 20, 21, 25, 27, 28, 32, 40, 68, 139, 157, 163 Epithelial Cells, 12, 15, 21, 27, 28, 32, 40, 68, 157, 163 Epithelium, 7, 10, 21, 22, 25, 28, 77, 156, 157, 168, 178 Epitope, 7, 59, 157 Erection, 157, 165 ERV, 120, 157, 158 Erythrocyte Indices, 146, 157 Erythrocytes, 142, 146, 157 Esophageal, 65, 76, 108, 157 Esophagus, 154, 157, 162, 170, 179, 185, 191 Estrogen, 10, 46, 48, 68, 157, 182 Eukaryotic Cells, 157, 165, 177 Evoke, 157, 191 Excitation, 158, 176 Excrete, 158, 186 Exocrine, 3, 4, 12, 16, 19, 24, 31, 36, 52, 158, 177 Exogenous, 156, 158, 160 Expiratory, 157, 158 Expiratory Reserve Volume, 157, 158 Extensor, 158, 197 External-beam radiation, 158, 168, 184, 198 Extracellular, 20, 22, 37, 52, 59, 141, 145, 151, 156, 158, 159, 166, 171, 173, 190 Extracellular Matrix, 151, 158, 159, 166, 171 Extracellular Matrix Proteins, 158, 171 Eye Infections, 139, 158 Eye socket, 158, 179 F Facial, 158, 178 Facial Nerve, 158, 178 Fallopian tube, 158, 195 Family Planning, 119, 158 Fat, 143, 145, 146, 150, 152, 158, 169, 174, 186, 190 Fatigue, 33, 53, 54, 75, 84, 102, 106, 158, 162 Fatty acids, 85, 140, 158, 182 Fetal Heart, 17, 159

203

Fetus, 159, 180, 196 Fibroblasts, 151, 159, 167 Fibrosis, 19, 159, 187, 188 Filtration, 56, 159 Fluoxetine, 88, 159 Fold, 33, 159 Follicles, 48, 159 Foramen, 149, 159 Forearm, 146, 159 Friction, 159, 170 Fungi, 158, 159, 172, 193, 198 Fungus, 147, 159 G Gallbladder, 139, 145, 154, 159 Gallstones, 145, 149, 159, 196 Gamma Rays, 159, 184, 185 Ganglia, 139, 144, 159, 175, 179 Gas, 141, 157, 159, 163, 165, 174, 176, 192, 197 Gastric, 39, 42, 54, 80, 144, 157, 159, 162 Gastrin, 159, 163 Gastritis, 55, 108, 160 Gastroenterologist, 108, 160 Gastrointestinal, 22, 39, 53, 55, 108, 157, 160, 188, 192 Gastrointestinal tract, 108, 160, 188 Gene, 9, 10, 11, 13, 21, 22, 24, 26, 29, 35 Gene Expression, 11, 13, 22, 24, 77, 160 Gene Targeting, 29, 160 Gene Therapy, 139, 160 Genetic Code, 160, 176 Genetics, 11, 21, 26, 29, 76, 160 Genomics, 12, 160 Genotype, 26, 160, 179 Germ Cells, 160, 176, 190 Germinal Center, 42, 43, 48, 160 Giant Cells, 160, 187 Glomerulus, 160, 175 Glucocorticoid, 160, 182 Glucose, 26, 97, 148, 154, 161, 162, 166, 187 Glucose Intolerance, 26, 154, 161 Glucose tolerance, 97, 161 Glucose Tolerance Test, 97, 161 Glutamic Acid, 161, 176, 182 Gluten, 108, 148, 161 Glycerol, 143, 161, 179 Glycine, 141, 145, 149, 161, 176, 188 Glycoprotein, 160, 161, 193, 195 Gonadal, 161, 191 Governing Board, 161, 181 Grade, 65, 73, 102, 161 Graft, 14, 44, 93, 94, 161, 163

Graft-versus-host disease, 44, 161 Gram-positive, 161, 169 Granule, 6, 68, 161, 187 Granulocytes, 161, 169, 189, 198 Growth, 8, 12, 17, 20, 21, 27, 84, 103, 142, 143, 146, 148, 157, 161, 162, 163, 167, 171, 175, 180, 184, 186, 193, 195, 196 Growth factors, 17, 27, 162 H Haplotypes, 60, 162 Haptens, 140, 162 Headache, 97, 162 Headache Disorders, 162 Heart failure, 30, 86, 162 Heartburn, 102, 108, 162, 165 Hematocrit, 146, 157, 162 Hemodynamics, 162, 168 Hemoglobin, 142, 146, 157, 162 Hemophilia, 82, 162 Hemorrhage, 152, 162, 184, 191 Hemostasis, 162, 167, 188 Hepatic, 29, 37, 86, 140, 161, 162 Hepatitis, 39, 56, 57, 61, 65, 70, 79, 82, 162, 163 Hepatitis C, 39, 57, 163 Hepatocytes, 162, 163 Hereditary, 101, 151, 162, 163, 180, 184 Heredity, 160, 163 Heterodimer, 146, 163 Heterogeneity, 140, 163 Histology, 10, 87, 163 Homeostasis, 20, 26, 30, 163 Homodimer, 163, 195 Homogeneous, 11, 163 Homologous, 59, 140, 160, 163, 188, 192 Hormonal, 5, 8, 14, 27, 86, 96, 97, 143, 152, 163, 197 Hormone, 10, 94, 139, 140, 152, 157, 159, 163, 166, 182, 186, 188, 189, 193, 195, 197 Hormone Replacement Therapy, 10, 163 Host, 13, 14, 93, 94, 144, 147, 163, 164, 186 Human papillomavirus, 52, 163 Hybrid, 23, 150, 163 Hybridization, 10, 15, 29, 163 Hybridomas, 163, 167 Hydration, 6, 163 Hydrogen, 139, 144, 147, 158, 163, 164, 170, 173, 176, 177, 179, 184 Hydrogen Bonding, 164, 176 Hydrogen Peroxide, 164, 170 Hydrolysis, 164, 169, 179, 183 Hydroxylysine, 150, 164

204

Sjogren's syndrome

Hydroxyproline, 141, 150, 164 Hyperbilirubinemia, 164, 168 Hyperplasia, 102, 164 Hypersensitivity, 140, 156, 164, 186 Hypersplenism, 66, 164 Hypertension, 162, 164, 194, 196 Hypertrophy, 164 Hypnotic, 144, 164, 193 Hypophysis, 59, 164 I Id, 90, 124, 127, 134, 136, 164 Idiopathic, 19, 28, 29, 164, 187 Immune function, 164, 165, 195 Immune response, 9, 13, 94, 142, 144, 152, 162, 164, 165, 171, 188, 192, 197 Immune Sera, 164, 165 Immune system, 8, 9, 18, 82, 94, 95, 97, 109, 144, 145, 164, 165, 170, 171, 174, 196, 198 Immunity, 59, 164, 194 Immunization, 7, 32, 164 Immunoassay, 33, 165 Immunofluorescence, 17, 33, 165 Immunoglobulin, 35, 40, 44, 142, 165, 173 Immunologic, 9, 33, 60, 80, 103, 164, 165, 185 Immunology, 37, 42, 43, 44, 47, 48, 50, 51, 60, 64, 78, 82, 83, 86, 140, 165 Immunosuppressant, 165, 172 Immunosuppressive, 8, 33, 153, 160, 165, 188 Immunosuppressive Agents, 165, 188 Impaction, 6, 165 Impairment, 5, 10, 19, 143, 158, 165, 172 Implant radiation, 165, 167, 168, 184, 198 Impotent, 34, 165 In situ, 10, 103, 165 In Situ Hybridization, 10, 165 In vitro, 18, 20, 21, 22, 28, 33, 39, 52, 85, 160, 165 In vivo, 6, 7, 8, 14, 20, 21, 23, 33, 34, 85, 160, 165 Incision, 94, 165, 167 Incontinence, 165, 174 Indicative, 165, 178, 197 Indigestion, 108, 165 Indomethacin, 14, 165 Induction, 20, 22, 32, 142, 165, 182 Infancy, 166, 184, 187 Infarction, 152, 166, 172 Infertility, 96, 166 Infiltration, 4, 11, 14, 27, 31, 62, 72, 166

Ingestion, 161, 166, 181 Initiation, 18, 19, 31, 166 Innervation, 44, 158, 166 Inorganic, 166, 174 Insight, 14, 25, 30, 166 Insulator, 166, 174 Insulin, 60, 161, 166 Insulin-dependent diabetes mellitus, 166 Integrins, 79, 166 Interferon, 11, 13, 51, 62, 167 Interferon-alpha, 167 Interleukin-1, 25, 32, 43, 55, 68, 167 Interleukin-10, 55, 68, 167 Interleukin-2, 41, 167 Interleukin-6, 49, 167 Intermittent, 155, 167 Internal Medicine, 31, 82, 84, 86, 88, 156, 167, 187 Internal radiation, 167, 168, 184, 198 Interphase, 18, 167 Interstitial, 62, 65, 68, 78, 146, 167, 168, 175, 186, 198 Intestinal, 36, 87, 148, 149, 161, 167, 169, 171, 197 Intestinal Mucosa, 148, 167 Intestine, 145, 146, 167, 169 Intoxication, 86, 167, 184 Intracellular, 8, 12, 17, 24, 28, 30, 32, 150, 166, 167, 183, 185, 189 Intravenous, 54, 167 Intrinsic, 23, 140, 143, 167 Inulin, 155, 167 Invasive, 164, 167, 171 Ions, 6, 139, 144, 154, 155, 163, 168 Ion-Selective Electrodes, 6, 168 Iris, 152, 168, 184, 196 Irradiation, 26, 30, 168, 198 Irritants, 22, 168 Ischemia, 143, 168, 174 Isotonic, 6, 29, 168 J Jaundice, 108, 164, 168 Joint, 16, 53, 64, 143, 168, 192 K Kallikrein-Kinin System, 63, 168 Kb, 118, 168 Keratoconjunctivitis, 25, 63, 83, 87, 88, 93, 96, 97, 113, 127, 128, 129, 137, 168, 189 Keratoconjunctivitis Sicca, 25, 83, 87, 88, 93, 96, 97, 127, 128, 129, 168, 189 Keratolytic, 153, 168 Kinesin, 18, 169

205

L Lacrimal gland, 3, 6, 8, 10, 11, 14, 16, 17, 18, 21, 23, 27, 32, 34, 41, 45, 56, 86, 169 Lactation, 27, 150, 169, 182 Lactobacillus, 4, 169 Large Intestine, 154, 167, 169, 185, 189 Laryngeal, 76, 169 Larynx, 169, 194 Latent, 169, 182 Laxative, 140, 149, 169, 172 Lens, 17, 143, 147, 148, 169 Lethal, 144, 169, 174 Leucocyte, 156, 169 Leukocytes, 14, 144, 146, 149, 161, 165, 167, 169, 174, 195 Libido, 142, 169 Library Services, 134, 169 Ligands, 166, 169 Ligation, 96, 169 Linkage, 129, 169 Lip, 50, 58, 64, 91, 92, 94, 169 Lipid, 45, 84, 161, 166, 169, 170, 174 Lipid Peroxidation, 84, 170 Liver, 28, 33, 36, 96, 103 Liver Transplantation, 33, 170 Localized, 141, 153, 166, 170, 174, 180, 188, 195 Loop, 27, 37, 52, 170 Lower Esophageal Sphincter, 108, 170 Lubricants, 170 Lubrication, 21, 34, 170 Lumen, 27, 156, 170 Lupus, 9, 11, 23, 28, 34, 35, 37, 52, 65, 80, 83, 93, 94, 95, 107, 125, 127, 170, 193 Lutein Cells, 170, 182 Lymph, 32, 156, 170, 187, 192 Lymph node, 32, 170, 187 Lymphatic, 156, 166, 170, 172, 191, 193 Lymphatic system, 170, 191, 193 Lymphocyte, 6, 18, 23, 61, 68, 79, 142, 170, 171 Lymphocytic, 4, 11, 14, 16, 23, 27, 31, 32, 65, 170 Lymphoid, 39, 42, 48, 51, 66, 142, 160, 169, 170, 171 Lymphoma, 13, 39, 42, 50, 51, 57, 60, 65, 66, 68, 71, 80, 83, 86, 92, 170, 171 Lymphoproliferative, 64, 170 Lytic, 170, 188 M Macrophage, 167, 171 Magnetic Resonance Imaging, 82, 103, 171

Major Histocompatibility Complex, 162, 171 Malabsorption, 109, 148, 171 Malignant, 102, 103, 139, 143, 171, 175, 185 Malignant tumor, 103, 171 Malnutrition, 30, 140, 143, 171 MALT lymphoma, 41, 46, 57, 171 Mammary, 150, 171 Mandible, 149, 171 Mastication, 19, 171 Matrix metalloproteinase, 25, 34, 47, 49, 87, 171 Mediate, 10, 25, 154, 171 Mediator, 167, 171, 188 MEDLINE, 119, 171 Meibomian, 10, 45, 171 Meibomian Glands, 10, 171 Melanin, 154, 168, 171, 179, 195 Membrane, 7, 8, 12, 17, 18, 22, 25, 29, 85, 143, 144, 148, 150, 151, 154, 156, 157, 158, 164, 169, 171, 174, 175, 177, 179, 183, 186, 189, 192 Memory, 13, 47, 142, 160, 171 Meninges, 148, 152, 172 Menopause, 10, 172, 181 Menstrual Cycle, 172, 182 Menstruation, 172 Mental, iv, 5, 66, 99, 118, 120, 149, 154, 158, 171, 172, 184, 196 Mental Disorders, 99, 172, 184 Mental Health, iv, 5, 99, 118, 120, 172, 184 Mercury, 172, 184 Mesenchymal, 157, 172 Metaplasia, 35, 172 Metastasis, 171, 172 Methotrexate, 50, 172 Methylcellulose, 85, 172 MI, 138, 172 Mice Minute Virus, 172, 178 Microbe, 22, 172, 194 Microorganism, 150, 172, 197 Micro-organism, 153, 172 Microscopy, 14, 17, 28, 33, 172 Microtubules, 18, 169, 173 Migration, 13, 14, 18, 173 Milliliter, 146, 173 Mineralization, 173, 177 Mineralocorticoids, 139, 152, 173 Miotic, 173, 180 Mitochondria, 173, 177 Mitogen-Activated Protein Kinase Kinases, 173

206

Sjogren's syndrome

Mitogen-Activated Protein Kinases, 24, 173 Mitosis, 25, 143, 173 Modification, 141, 173, 184 Molecule, 21 Monitor, 5, 27, 32, 173, 176 Monoclonal, 24, 39, 163, 168, 173, 184, 187, 198 Monoclonal antibodies, 24, 173, 187 Monocytes, 167, 169, 174, 193 Mononuclear, 11, 23, 83, 174, 195 Morphogenesis, 12, 21, 174 Morphological, 30, 155, 159, 174 Morphology, 44, 148, 174 Motility, 19, 165, 174, 188 Motion Sickness, 174, 175 Mouth Ulcer, 94, 174 Mucins, 22, 25, 174, 187 Mucosa, 39, 42, 66, 170, 171, 174, 175, 182 Mucositis, 5, 102, 174 Mucus, 6, 22, 102, 103, 127, 174 Multiple sclerosis, 26, 58, 174 Muscarinic Agonists, 78, 89, 174 Muscle Contraction, 108, 174 Mustard Gas, 168, 174 Myelin, 174, 188 Myelitis, 76, 174 Myocardial Contraction, 30, 174 Myocardium, 172, 175 Myosin, 174, 175 Myositis, 70, 86, 175 N Nasal Cavity, 175 Nasal Mucosa, 75, 175 Natural selection, 145, 175 Nausea, 97, 165, 175, 196 NCI, 1, 98, 117, 175 Need, 3, 33, 101, 102, 107, 109, 113, 130, 171, 175, 194 Neonatal, 23, 42, 75, 93, 175 Neoplasia, 175 Neoplasm, 175, 195 Neoplastic, 42, 102, 141, 163, 170, 175 Nephritis, 62, 175 Nephron, 160, 168, 175 Nerve, 32, 96 Nerve Endings, 32, 175 Nervous System, 39, 43, 62, 88, 148, 171, 175, 176, 179 Networks, 12, 175, 193 Neural, 32, 141, 175 Neuroeffector Junction, 175

Neuromuscular, 139, 176, 196 Neuromuscular Junction, 139, 176 Neurons, 159, 175, 176, 192 Neuropathy, 66, 74, 82, 176, 179 Neurotransmitter, 32, 139, 141, 154, 161, 176, 189, 192 Neutrons, 141, 168, 176, 184 Neutrophil, 6, 84, 176 Nitrogen, 140, 142, 153, 158, 176, 195 Norepinephrine, 140, 154, 176 Nuclear, 9, 16, 20, 51, 79, 87, 144, 157, 159, 176, 196 Nuclei, 141, 160, 171, 173, 176, 177, 184, 193 Nucleic acid, 28, 160, 163, 165, 176, 187 Nucleic Acid Hybridization, 29, 163, 176 Nucleus, 143, 144, 149, 153, 157, 159, 174, 176, 182, 184, 191, 193 Nursing Care, 176, 178 O Ocular, 8, 10, 14, 17, 18, 22, 23, 25, 31, 34, 69, 83, 85, 176 Oncogenic, 167, 176 Oocytes, 7, 176 Opacity, 148, 153, 177 Ophthalmology, 23, 25, 27, 38, 43, 44, 56, 85, 86, 88, 124, 177 Optic Nerve, 177, 186, 187 Oral Health, 5, 30, 84, 92, 177 Oral Hygiene, 15, 69, 177 Orbit, 158, 177, 179 Organelles, 25, 150, 153, 169, 174, 177, 180 Osmosis, 177 Osmotic, 29, 140, 177 Osteomalacia, 72, 85, 86, 177 Osteoporosis, 94, 177 Otitis, 69, 177 Ovaries, 177, 189, 195 Ovum, 152, 177, 182 Oxidation, 139, 170, 177 P Palliative, 19, 34, 108, 177, 193 Pancreas, 27, 103, 139, 154, 166, 177, 178, 188 Pancreatic, 178 Pancreatitis, 108, 178 Papillomavirus, 178 Parotid, 24, 27, 31, 41, 51, 76, 85, 88, 178, 187 Parotitis, 73, 178 Partial remission, 178, 186 Parturition, 178, 182

207

Parvovirus, 67, 172, 178 Pathogenesis, 3, 5, 6, 7, 10, 12, 14, 17, 23, 24, 25, 31, 65, 72, 178 Pathologic, 22, 139, 143, 145, 147, 152, 164, 178 Pathologic Processes, 143, 178 Pathologies, 8, 178 Pathology, Oral, 49, 54, 72, 87, 178 Pathophysiology, 34, 86, 178 Patient Care Management, 108, 178 Patient Education, 4, 108, 125, 129, 132, 134, 138, 178 Penicillamine, 89, 178 Penicillin, 178, 196 Pepsin, 178, 188 Peptide, 6, 49, 141, 178, 183 Perennial, 155, 178 Perforation, 10, 159, 178 Pericardium, 178, 192 Periodontitis, 15, 179 Periorbital, 21, 179 Peripheral blood, 11, 42, 47, 62, 84, 85, 167, 179 Peripheral Nervous System, 156, 176, 179, 182, 192 Peripheral Neuropathy, 60, 82, 179 Peripheral stem cells, 161, 179 Petrolatum, 155, 179 PH, 46, 146, 179 Pharmacologic, 142, 143, 179, 194 Pharynx, 93, 164, 175, 179 Phenolphthalein, 155, 179 Phenotype, 7, 11, 23, 62, 179 Phenylalanine, 179, 195 Phorbol, 179, 183 Phorbol Esters, 179, 183 Phospholipases, 179, 189 Phospholipids, 158, 179, 183 Phosphorus, 147, 179, 180 Phosphorylates, 179, 183 Phosphorylation, 13, 15, 30, 31, 49, 173, 179, 183 Physical Examination, 92, 94, 95, 96, 97, 103, 180 Physiologic, 14, 140, 167, 168, 172, 180, 182, 185 Physiology, 8, 14, 19, 24, 27, 139, 155, 156, 180 Pilocarpine, 4, 5, 69, 78, 83, 87, 88, 102, 106, 112, 113, 180 Pilot study, 26, 50, 83, 87, 89, 96, 180 Pituitary Gland, 152, 180

Placenta, 180, 182 Plants, 140, 147, 149, 161, 167, 174, 176, 180, 187, 194 Plaque, 15, 149, 180 Plasma, 8, 13, 49, 62, 63, 140, 142, 145, 148, 156, 161, 162, 173, 180, 185, 186 Plasma cells, 62, 142, 180 Plasma protein, 140, 156, 180 Plasmids, 7, 180 Plasticity, 21, 180 Plastids, 177, 180 Platelet Activation, 180, 189 Platinum, 170, 180 Pneumonia, 68, 78, 152, 181 Pneumonitis, 65, 181 Poisoning, 167, 172, 175, 181 Polyarthritis, 168, 181, 189 Polymerase, 34, 181 Polymers, 145, 181, 183 Polymorphic, 26, 181 Polymorphism, 49, 59, 61, 70, 181 Polysaccharide, 142, 148, 181 Posterior, 143, 168, 177, 181, 187 Postmenopausal, 10, 177, 181 Postnatal, 181, 191 Postsynaptic, 175, 181, 189 Potentiate, 20, 181 Potentiation, 181, 189 Practice Guidelines, 120, 181 Precancerous, 92, 181, 182 Precipitation, 181 Precipitins, 11, 181 Precursor, 143, 146, 153, 154, 155, 156, 176, 179, 181, 195, 196, 197 Predisposition, 6, 182 Prednisolone, 14, 69, 182 Premalignant, 181, 182 Preoperative, 103, 182 Presynaptic, 175, 176, 182 Presynaptic Terminals, 175, 182 Prevalence, 23, 26, 29, 50, 70, 72, 108, 182 Primary Biliary Cirrhosis, 53, 68, 76, 83, 108, 182 Probe, 20, 182 Progesterone, 10, 48, 182, 191 Progression, 31, 32, 142, 182 Progressive, 11, 33, 37, 97, 148, 149, 155, 161, 180, 182, 186, 195 Prolactin, 8, 27, 40, 182 Proline, 150, 164, 182 Promoter, 22, 45, 49, 52, 55, 68, 182 Prone, 28, 108, 182

208

Sjogren's syndrome

Prophase, 176, 182, 192 Prostaglandin, 84, 182 Prostaglandins A, 165, 183 Protein C, 14, 140, 141, 144, 150, 183, 196 Protein Conformation, 141, 183 Protein Kinase C, 24, 173, 183 Protein Kinases, 14, 24, 173, 183 Protein S, 8, 9, 14, 17, 32, 146, 160, 183, 187 Protein Subunits, 14, 183 Protein-Serine-Threonine Kinases, 173, 183 Proteolytic, 8, 146, 150, 183 Protocol, 9, 93, 95, 183 Protons, 141, 163, 184 Pruritus, 33, 184, 196 Pseudohypoaldosteronism, 6, 184 Psychiatric, 67, 172, 184 Psychiatry, 74, 88, 184 Psychic, 169, 172, 184 Ptyalism, 102, 184, 187 Public Health, 21, 120, 184 Public Policy, 119, 184 Pulmonary, 68, 71, 106, 146, 157, 184 Pulmonary Artery, 146, 184 Pulse, 173, 184 Pupil, 152, 173, 184 Purpura, 39, 63, 184 Q Quality of Life, 30, 48, 57, 184 Quiescent, 184, 197 R Race, 9, 173, 184 Radiation, 19, 92, 158, 159, 167, 168, 184, 185, 198 Radiation therapy, 19, 158, 167, 168, 184, 198 Radioactive, 163, 165, 167, 168, 174, 176, 184, 185, 193, 196, 198 Radiolabeled, 168, 184, 185, 198 Radiotherapy, 146, 168, 184, 185, 198 Randomized, 155, 185 Ranula, 102, 185 Receptor, 7, 8, 14, 16, 17, 24, 30, 32, 35, 85 Receptors, Muscarinic, 174, 185 Receptors, Serotonin, 185, 188 Recombinant, 16, 29, 32, 185, 197 Recombination, 160, 185 Reconstitution, 7, 10, 185 Rectum, 146, 150, 154, 159, 165, 169, 185 Red Nucleus, 143, 185 Reductase, 172, 185

Refer, 1, 147, 150, 154, 156, 159, 170, 176, 185, 194 Reflux, 108, 185 Refraction, 185, 190 Regeneration, 185 Regimen, 155, 185 Regurgitation, 44, 162, 185 Reliability, 5, 186 Remission, 186 Renal failure, 145, 186, 196 Renal tubular, 45, 72, 86, 186 Renal tubular acidosis, 45, 72, 86, 186 Renin, 168, 186 Respiration, 173, 186 Restoration, 152, 185, 186, 198 Retina, 169, 177, 186, 187, 196 Retinal, 177, 186, 197 Retrospective, 36, 186 Retrovirus, 28, 106, 186 Rheumatism, 3 Rheumatoid, 5, 11, 16, 21, 26, 34, 84, 86, 88, 93, 94, 95, 124, 129 Rheumatoid arthritis, 11, 21, 26, 34, 84, 86, 88, 94, 95, 129 Rheumatology, 5, 82, 83, 84, 85, 86, 87, 88, 89, 93, 125 Ribonuclease, 10, 187 Ribonucleic acid, 187 Ribonucleoproteins, 16, 187 Ribosome, 187, 195 Rickets, 187, 197 Risk factor, 73, 187 Rituximab, 51, 60, 187 Rod, 144, 169, 187 S Saliva, 4, 13, 15, 19, 29, 87, 91, 92, 94, 95, 96, 103, 108, 109, 126, 127 Salivary Gland Neoplasms, 102, 187 Salivary glands, 4, 12, 20, 21, 23, 24, 28, 29, 32, 41, 43, 46, 47, 49, 50, 51, 68, 77, 79, 83, 87, 89, 91, 92, 94, 95, 102, 128, 154, 158, 187, 189 Salivation, 102, 187 Saponins, 187, 191 Sarcoidosis, 37, 56, 103, 187 Scalpel, 76, 187 Sclera, 14, 151, 157, 187, 196 Scleritis, 14, 187 Scleroderma, 33, 53, 93, 124, 188 Sclerosis, 26, 37, 42, 84, 150, 174, 188 Screening, 4, 80, 92, 94, 150, 188, 196 Sebaceous, 168, 171, 188

209

Sebaceous gland, 168, 171, 188 Secretin, 127, 188 Secretory, 7, 8, 14, 18, 20, 22, 28, 30, 36, 85, 176, 188 Sediment, 188, 196 Segregation, 25, 144, 185, 188 Senile, 177, 188 Sensory loss, 174, 188, 193 Sequence Homology, 28, 188 Sequencing, 22, 188 Serine, 173, 183, 188 Serologic, 4, 165, 188 Serotonin, 52, 159, 176, 185, 188, 195 Serous, 150, 156, 188 Serum, 10, 13, 16, 26, 28, 33, 36, 61, 65, 70, 140, 145, 150, 164, 168, 173, 185, 188, 195 Sex Characteristics, 142, 189, 193 Sharpness, 189, 197 Shedding, 17, 189 Shock, 189, 195 Sialography, 103, 189 Sialorrhea, 102, 189 Sicca, 3, 9, 25, 28, 34, 36, 63, 69, 74, 78, 83, 87, 88, 93, 96, 97, 107, 127, 128, 129, 137, 189 Side effect, 19, 34, 94, 95, 96, 102, 111, 113, 140, 145, 153, 189, 194 Signal Transduction, 7, 13, 189 Signs and Symptoms, 92, 108, 186, 189, 196 Skeletal, 26, 142, 189 Skeleton, 139, 168, 182, 189 Small intestine, 149, 155, 163, 167, 189 Smooth muscle, 143, 151, 174, 189, 192, 197 Sneezing, 189 Social Environment, 184, 189 Sodium, 4, 83, 140, 168, 173, 184, 190, 192 Soft tissue, 15, 91, 92, 146, 189, 190 Solvent, 161, 177, 190 Soma, 190 Somatic, 9, 173, 179, 190 Somatic cells, 173, 190 Somatic mutations, 9, 190 Somnolence, 61, 190 Sound wave, 151, 190 Spatial disorientation, 154, 190 Specialist, 129, 190 Species, 15, 148, 157, 163, 169, 172, 173, 178, 180, 184, 188, 190, 192, 193, 195, 197, 198 Specificity, 34, 140, 190

Spectrum, 8, 190 Sperm, 142, 149, 190, 195 Sphincter, 108, 169, 190 Spinal cord, 148, 149, 152, 172, 174, 175, 176, 179, 190 Spinal Cord Vascular Diseases, 174, 190 Spleen, 141, 170, 187, 191 Splenectomy, 164, 191 Splenomegaly, 66, 164, 191 Squamous, 35, 191 Stabilizer, 14, 191 Stasis, 6, 191 Stem cell transplantation, 57, 191 Stem Cells, 93, 179, 191 Sterile, 92, 191 Sterility, 153, 166, 191 Steroid, 10, 145, 152, 187, 191 Stimulant, 45, 191, 196 Stimulants, 108 Stimulus, 17, 82, 158, 166, 191 Stomach, 97, 108, 139, 144, 154, 157, 159, 160, 161, 163, 170, 175, 178, 179, 185, 188, 189, 191, 198 Stool, 150, 165, 169, 191 Strand, 64, 181, 191 Stress, 25, 152, 173, 175, 182, 186, 191 Stroke, 99, 118, 125, 126, 191 Stroma, 49, 168, 191 Subacute, 23, 166, 191 Subarachnoid, 162, 191 Subclinical, 166, 191 Sublingual, 24, 185, 191 Submandibular, 24, 82, 192 Submaxillary, 157, 185, 192 Subspecies, 190, 192 Substance P, 185, 188, 192 Suction, 92, 159, 192 Supplementation, 10, 192 Support group, 128, 192 Suppression, 87, 152, 192 Sweat, 6, 192 Sweat Glands, 192 Symphysis, 149, 192 Symptomatic, 67, 178, 192 Synapse, 140, 175, 176, 182, 192, 195 Synaptic, 176, 189, 192 Synergistic, 182, 192 Synovial, 192 Synovial Membrane, 192 Synovitis, 64, 192 Systemic disease, 30, 192

210

Sjogren's syndrome

Systemic lupus erythematosus, 9, 11, 28, 34, 52, 53, 75, 78, 83, 94, 95, 107, 150, 192 T Tear Gases, 168, 193 Technetium, 46, 193 Telophase, 25, 193 Testosterone, 8, 185, 193 Thalamic, 143, 193 Thalamic Diseases, 143, 193 Thalidomide, 95, 193 Therapeutics, 26, 112, 193 Threonine, 173, 183, 188, 193 Thrombin, 183, 193 Thrombocytopenia, 39, 86, 193 Thrombomodulin, 183, 193 Thrombosis, 167, 183, 191, 193 Thrush, 5, 147, 193 Thymus, 39, 165, 170, 193 Thyroid, 9, 59, 76, 193, 195 Thyroid Gland, 193 Thyroiditis, 28, 33, 56, 193 Thyroxine, 140, 179, 193 Tin, 179, 180, 194 Tinnitus, 177, 194 Tolerance, 8, 97, 139, 161, 194 Tomography, 51, 103, 151, 194 Tone, 174, 177, 194 Tonicity, 168, 194 Tooth Loss, 109, 194 Topical, 14, 108, 149, 164, 179, 194 Toxic, iv, 31, 153, 164, 176, 194 Toxicity, 154, 172, 194 Toxicology, 20, 120, 194 Toxin, 42, 156, 194 Trachea, 169, 179, 193, 194 Transcriptase, 186, 194 Transduction, 7, 13, 17, 189, 194 Transfection, 146, 160, 194 Transfer Factor, 165, 194 Transforming Growth Factor beta, 38, 84, 195 Transfusion, 163, 195 Transgenes, 32, 195 Translation, 39, 141, 195 Translocation, 54, 195 Transmitter, 139, 154, 171, 176, 195 Transplantation, 33, 63, 94, 165, 171, 195 Trauma, 8, 103, 178, 195, 198 Tryptophan, 150, 188, 195 Tubal ligation, 96, 195 Tubulin, 173, 195 Tumor Necrosis Factor, 38, 87, 193, 195

Tumour, 62, 70, 195 Tunica, 174, 195 Tyrosine, 13, 154, 195 U Ulcer, 195 Ulceration, 10, 21, 195 Unconscious, 153, 164, 195 Uraemia, 178, 196 Uranium, 193, 196 Urea, 192, 196 Ureters, 196 Urethra, 196 Urinalysis, 94, 196 Urinary, 39, 61, 62, 144, 153, 165, 174, 184, 196 Urinary tract, 39, 61, 144, 196 Urine, 94, 96, 97, 144, 145, 146, 157, 165, 196 Ursodeoxycholic Acid, 33, 196 Uterus, 152, 172, 177, 182, 195, 196 Uvea, 196 Uveitis, 14, 59, 196 V Vaccine, 183, 196 Vacuoles, 156, 177, 196 Vagina, 95, 147, 169, 172, 196 Vaginal, 102, 170, 196 Vaginitis, 147, 196 Valine, 178, 196 Vascular, 14, 54, 79, 89, 156, 162, 166, 180, 190, 193, 196, 197 Vasculitis, 57, 62, 178, 197 Vasopressins, 168, 197 Vector, 194, 197 Vein, 97, 167, 176, 178, 197 Venous, 146, 183, 197 Venous blood, 146, 197 Venules, 146, 147, 156, 197 Vertigo, 177, 197 Veterinary Medicine, 119, 197 Villous, 148, 197 Viral, 29, 79, 160, 176, 186, 194, 197 Viral Proteins, 29, 197 Virus, 29, 35, 50, 56, 57, 61, 65, 70, 79, 144, 148, 160, 163, 167, 180, 194, 197 Visual Acuity, 10, 188, 197 Vitamin D, 85, 187, 197 Vitiligo, 38, 197 Vitreous, 169, 186, 197 Vitro, 18, 20, 21, 22, 28, 33, 85, 197 Vivo, 6, 7, 8, 14, 20, 21, 24, 33, 34, 85, 197

211

W Warts, 163, 197 Watermelon Stomach, 54, 198 White blood cell, 142, 150, 169, 170, 171, 174, 176, 180, 198 Windpipe, 179, 193, 198 Wound Healing, 34, 167, 171, 198 X Xenograft, 142, 198 Xerophthalmia, 3, 16, 198

Xerostomia, 3, 4, 16, 19, 26, 30, 82, 85, 86, 91, 92, 94, 95, 101, 102, 108 X-ray, 30, 96, 146, 151, 152, 159, 168, 176, 184, 185, 191, 198 X-ray therapy, 168, 198 Y Yeasts, 147, 159, 179, 198 Z Zymogen, 183, 198

212

Sjogren's syndrome